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1.
Sunay, Melek ME.
Harnessing Mechanisms of Immune Modulation by Sorafenib to Augment the Efficacy of Cellular Immunotherapy.
Degree: 2015, Johns Hopkins University
URL: http://jhir.library.jhu.edu/handle/1774.2/38006
► The tumor microenvironment is established and maintained through the complex interactions of tumor cells with host stromal elements. Therefore, therapies that target multiple cellular components…
(more)
▼ The tumor microenvironment is established and maintained through the complex interactions of tumor cells with host stromal elements. Therefore, therapies that target multiple cellular components of the tumor may be most effective. Sorafenib, a multi-kinase inhibitor, alters signaling pathways in tumor cells and host stromal cells. Thus, we explored the potential immune-modulating effects of Sorafenib in a murine HER-2-(neu) overexpressing breast tumor model alone and in combination with a HER-2 targeted granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting vaccine. In vitro, Sorafenib inhibited the growth of HER-2 overexpressing NT2.5 tumor cells, inducing apoptosis. Western blot analysis revealed that Sorafenib interfered with ERK MAPK, p38 MAPK, and STAT3 signaling, but not HER-2 or Akt signaling. It also decreased D-type cyclin expression. In vivo, single agent Sorafenib disrupted the tumor-associated vasculature and induced tumor apoptosis,
effectively inducing the regression of established NT2.5 tumors in immune competent FVB/N mice. Immune depletion studies demonstrated that tumor rejection was mediated by both CD4+ and CD8+ T cells. Sorafenib treatment enhanced tumor clearance induced by vaccination with a GM-CSF-secreting, HER-2-expressing cellular vaccine in tumor-bearing FVB/N mice relative to either drug treatment or vaccination alone. Although the magnitude of the peripheral antigen-specific T cell response was unchanged, Sorafenib appeared to enhance antigen-specific T cell accumulation at the tumor site. Overall, these findings suggest that dendritic cell-based
immunotherapy can be integrated with Sorafenib, resulting in enhanced therapeutic response.
Advisors/Committee Members: Scott, Allan (advisor).
Subjects/Keywords: immunotherapy. cancer
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APA (6th Edition):
Sunay, M. M. (2015). Harnessing Mechanisms of Immune Modulation by Sorafenib to Augment the Efficacy of Cellular Immunotherapy. (Thesis). Johns Hopkins University. Retrieved from http://jhir.library.jhu.edu/handle/1774.2/38006
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sunay, Melek ME. “Harnessing Mechanisms of Immune Modulation by Sorafenib to Augment the Efficacy of Cellular Immunotherapy.” 2015. Thesis, Johns Hopkins University. Accessed March 05, 2021.
http://jhir.library.jhu.edu/handle/1774.2/38006.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sunay, Melek ME. “Harnessing Mechanisms of Immune Modulation by Sorafenib to Augment the Efficacy of Cellular Immunotherapy.” 2015. Web. 05 Mar 2021.
Vancouver:
Sunay MM. Harnessing Mechanisms of Immune Modulation by Sorafenib to Augment the Efficacy of Cellular Immunotherapy. [Internet] [Thesis]. Johns Hopkins University; 2015. [cited 2021 Mar 05].
Available from: http://jhir.library.jhu.edu/handle/1774.2/38006.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sunay MM. Harnessing Mechanisms of Immune Modulation by Sorafenib to Augment the Efficacy of Cellular Immunotherapy. [Thesis]. Johns Hopkins University; 2015. Available from: http://jhir.library.jhu.edu/handle/1774.2/38006
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Vanderbilt University
2.
Shae, Daniel.
Design and Optimization of ‘Smart’ Nanoparticles for Targeting of the STING Pathway with Applications in Cancer Immunotherapy.
Degree: PhD, Chemical Engineering, 2019, Vanderbilt University
URL: http://hdl.handle.net/1803/10674
► I detail the rational design and optimization of STING-NPs: a nanoparticle delivery platform that stimulates innate immunity and T cell activation through targeted activation of…
(more)
▼ I detail the rational design and optimization of STING-NPs: a nanoparticle delivery platform that stimulates innate immunity and T cell activation through targeted activation of the stimulator of interferon genes (STING) protein, a critical cytosolic immune sensor of oncogenesis that has historically been difficult to target due to the poor pharmacokinetic properties of its natural ligand, cGAMP. STING-NPs comprise self-assembling, pH responsive, and endosomolytic polymers and overcome delivery barriers associated with cGAMP delivery by facilitating the cellular uptake and endosomal escape of cGAMP, facilitating a 2-3 order of magnitude enhancement in drug potency.
Administration of STING-NPs in murine tumor models initiates a multifaceted pro-inflammatory program associated with type I interferon expression and recruitment of T cells into the tumor microenvironment, eliciting tumor suppression or complete rejection through both intratumoral and systemic administration routes. Strikingly, STING-NP treatment is capable of mediating rejection of primary tumor growth as well as generating systemic and long-lived antitumor immunity, manifesting in suppression of distal tumor growth and resistance to cancer cell rechallenge. Efficacy is improved with the addition of checkpoint blockade antibodies, demonstrating that STING-NP treatment can sensitize tumors to ICB. Finally, the activity of STING-NPs is validated in an ex vivo model of freshly resected human melanoma.
Advisors/Committee Members: Jeffrey C. Rathell (committee member), Scott A. Guelcher (committee member), Paul E. Laibinis (committee member), Justin M. Balko (committee member), John T. Wilson (Committee Chair).
Subjects/Keywords: Cancer Immunotherapy
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
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to Zotero / EndNote / Reference
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APA (6th Edition):
Shae, D. (2019). Design and Optimization of ‘Smart’ Nanoparticles for Targeting of the STING Pathway with Applications in Cancer Immunotherapy. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10674
Chicago Manual of Style (16th Edition):
Shae, Daniel. “Design and Optimization of ‘Smart’ Nanoparticles for Targeting of the STING Pathway with Applications in Cancer Immunotherapy.” 2019. Doctoral Dissertation, Vanderbilt University. Accessed March 05, 2021.
http://hdl.handle.net/1803/10674.
MLA Handbook (7th Edition):
Shae, Daniel. “Design and Optimization of ‘Smart’ Nanoparticles for Targeting of the STING Pathway with Applications in Cancer Immunotherapy.” 2019. Web. 05 Mar 2021.
Vancouver:
Shae D. Design and Optimization of ‘Smart’ Nanoparticles for Targeting of the STING Pathway with Applications in Cancer Immunotherapy. [Internet] [Doctoral dissertation]. Vanderbilt University; 2019. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/1803/10674.
Council of Science Editors:
Shae D. Design and Optimization of ‘Smart’ Nanoparticles for Targeting of the STING Pathway with Applications in Cancer Immunotherapy. [Doctoral Dissertation]. Vanderbilt University; 2019. Available from: http://hdl.handle.net/1803/10674
3.
Khare, Priyanka.
Attenuation of gonadotropin secreting tumors by
immunotherapy.
Degree: 2009, Jamia Hamdard University
URL: http://shodhganga.inflibnet.ac.in/handle/10603/37387
Subjects/Keywords: Immunotherapy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Khare, P. (2009). Attenuation of gonadotropin secreting tumors by
immunotherapy. (Thesis). Jamia Hamdard University. Retrieved from http://shodhganga.inflibnet.ac.in/handle/10603/37387
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Khare, Priyanka. “Attenuation of gonadotropin secreting tumors by
immunotherapy.” 2009. Thesis, Jamia Hamdard University. Accessed March 05, 2021.
http://shodhganga.inflibnet.ac.in/handle/10603/37387.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Khare, Priyanka. “Attenuation of gonadotropin secreting tumors by
immunotherapy.” 2009. Web. 05 Mar 2021.
Vancouver:
Khare P. Attenuation of gonadotropin secreting tumors by
immunotherapy. [Internet] [Thesis]. Jamia Hamdard University; 2009. [cited 2021 Mar 05].
Available from: http://shodhganga.inflibnet.ac.in/handle/10603/37387.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Khare P. Attenuation of gonadotropin secreting tumors by
immunotherapy. [Thesis]. Jamia Hamdard University; 2009. Available from: http://shodhganga.inflibnet.ac.in/handle/10603/37387
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Minnesota
4.
Murphy, Katherine Anne.
Immune-based tumor regression induced by Fc-OX40L in a murine model of glioma.
Degree: PhD, Molecular, Cellular, Developmental Biology and Genetics, 2012, University of Minnesota
URL: http://purl.umn.edu/151476
► Glioblastoma multiforme, the most aggressive form of glioma, is a lethal brain tumor with a dismal median survival of 15-19 months. Immunotherapy is a promising…
(more)
▼ Glioblastoma multiforme, the most aggressive form of glioma, is a lethal brain tumor with a dismal median survival of 15-19 months. Immunotherapy is a promising adjuvant therapy for malignant brain tumors. Lack of adequate, endogenous antigen presentation and the immune suppressive nature of the tumor microenvironment present significant hurdles that need to be overcome in order to mount an effective immune response, capable of tumor elimination. Vaccination with tumor-derived antigen has sought to overcome inadequate antigen presentation, yet has shown to been inefficient at complete tumor elimination. Functionally unresponsiveness, anergy, can be induced in immune cells when antigen recognition occurs without proper costimulation. To test if additional costimulation was necessary to achieve a functional immune response, costimulatory molecules 41BBL, CD80, GITRL and OX40L, fused to the Fc portion of human immunoglobulin, were tested in combination with tumor vaccine. Vaccine/Fc-OX40L yielded the most potent response resulting in complete tumor regression in the majority of animals and the generation of immunological memory capable of rapidly clearing tumor upon tumor rechallenge. Additionally, combining vaccine/Fc-OX40L with the standard of care chemotherapy resulted in regression of 100% of glioma tumors, however 80% of these animals developed fatal secondary lymphoid malignancy. These data demonstrate Fc-OX40L has incredibly potent activity against experimental gliomas relative to the other molecules tested. In addition, it reveals a potential hazard in combining mutagenic chemotherapeutics with immunotherapy.
Lymphocytes isolated from vaccine/Fc-OX40L treated animals had enhanced cytolytic activity and increased proliferative capacity, compared to controls. Additional analysis demonstrated a CD4 T cell, NK, and B cell dependent, and CD8 T cell independent mechanism of action. The presence of tumor reactive antibody in the serum of treated mice and deposition of antibody at the tumor site, combined with the observation that loss of the Fc receptor negatively affected the ability of animals to control tumor growth generated interest in antibody-mediated mechanisms. Tumor infiltration of perforin expressing NK, NKT, and neutrophil-like cells in vaccine/Fc-OX40L treated animals may provide a possible mechanism of tumor killing. Further understanding the necessary effector cells and mechanisms involved in tumor elimination will aid in the design of future immunotherapy approaches.
Subjects/Keywords: Cancer; Immunotherapy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Murphy, K. A. (2012). Immune-based tumor regression induced by Fc-OX40L in a murine model of glioma. (Doctoral Dissertation). University of Minnesota. Retrieved from http://purl.umn.edu/151476
Chicago Manual of Style (16th Edition):
Murphy, Katherine Anne. “Immune-based tumor regression induced by Fc-OX40L in a murine model of glioma.” 2012. Doctoral Dissertation, University of Minnesota. Accessed March 05, 2021.
http://purl.umn.edu/151476.
MLA Handbook (7th Edition):
Murphy, Katherine Anne. “Immune-based tumor regression induced by Fc-OX40L in a murine model of glioma.” 2012. Web. 05 Mar 2021.
Vancouver:
Murphy KA. Immune-based tumor regression induced by Fc-OX40L in a murine model of glioma. [Internet] [Doctoral dissertation]. University of Minnesota; 2012. [cited 2021 Mar 05].
Available from: http://purl.umn.edu/151476.
Council of Science Editors:
Murphy KA. Immune-based tumor regression induced by Fc-OX40L in a murine model of glioma. [Doctoral Dissertation]. University of Minnesota; 2012. Available from: http://purl.umn.edu/151476

University of Melbourne
5.
Segal Wasserman, Gabriela.
Underlying mechanisms of effective adoptive T cell therapy against a B cell lymphoma.
Degree: 2014, University of Melbourne
URL: http://hdl.handle.net/11343/42223
► The immune system protects the body from potential dangers and mediates the destruction of infected or tumoural cells. The elimination of these target cells is…
(more)
▼ The immune system protects the body from potential dangers and mediates the destruction of infected or tumoural cells. The elimination of these target cells is predominantly executed by cytotoxic CD8 + T cells (CTLs) that destroy any cell presenting their cognate antigen, namely infected or tumoural cells. CTLs have characteristics that make them attractive for adoptive T cell therapy (ACT). This type of therapy infuses tumour-specific CTLs into cancer patients and mediates tumour regression. So far, the results obtained with ACT in clinical trials have been promising, but this therapy is still not the standard of care and many factors that affect the outcome remain unknown.
To study the factors that affect ACT, our laboratory has previously established a tumour model based on a B-cell lymphoma, the Eμ-myc tumour. This tumour has been transfected with GFP or with GFP-OVA. Utilizing these tumours together with transgenic T cells against OVA (OT-I) for ACT, we established that one of the key factors for the success of ACT is the tumour burden. We have proven that a high amount of tumour cells in the host triggers a quick deletion and inactivation of the transferred OT-I CTLs, a process that has shown to be antigen specific and directly mediated by the tumour cells.
In this thesis, we studied several factors that determine the outcome of ACT to deepen the understanding of the characteristics and mechanisms of the T cell inactivation occurring after ACT. In chapter three, it was established that using CTLs with a low affinity against the target antigen OVA (OT-3 cells) as ACT, resulted in tumour elimination when the tumour load was low. In addition, we show the importance of the level of antigen expression within the tumour, as high levels are required for successful ACT outcomes. Finally, we study the role of the avidity of the tumour: T cell interaction for the inactivation process, and demonstrate that this is an irrelevant factor for the inactivation to occur.
One of the complications associated with ACT is autoimmunity triggered by the destruction of healthy tissue. To study the relationship between ACT and autoimmunity in chapter four, we utilize ACT in a system where the tumour antigen is shared with healthy tissue. We determine that it is possible to eliminate a tumour expressing a shared antigen when targeting utilizing ACT, but successful ACT includes healthy tissue destruction in this setting.
One of the factors limiting the outcomes of ACT in our model is the deletion of the T cells once in the tumour-bearing host. To further investigate this we image ACT in situ and visualize the deletion of the T cells in organs like spleen and LN in chapter five. We establish a system utilizing two-photon microscopy (TPM) and fluorescently tagged cells to visualize the motility of the transferred T cells in the LN and determine a correlation between lower motility and dysfunction of the T cells.
Tumours hijack tolerance mechanisms to avoid anti-tumour attack; a strategy that can compromise the results obtained with…
Subjects/Keywords: cancer; immunotherapy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Segal Wasserman, G. (2014). Underlying mechanisms of effective adoptive T cell therapy against a B cell lymphoma. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/42223
Chicago Manual of Style (16th Edition):
Segal Wasserman, Gabriela. “Underlying mechanisms of effective adoptive T cell therapy against a B cell lymphoma.” 2014. Doctoral Dissertation, University of Melbourne. Accessed March 05, 2021.
http://hdl.handle.net/11343/42223.
MLA Handbook (7th Edition):
Segal Wasserman, Gabriela. “Underlying mechanisms of effective adoptive T cell therapy against a B cell lymphoma.” 2014. Web. 05 Mar 2021.
Vancouver:
Segal Wasserman G. Underlying mechanisms of effective adoptive T cell therapy against a B cell lymphoma. [Internet] [Doctoral dissertation]. University of Melbourne; 2014. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/11343/42223.
Council of Science Editors:
Segal Wasserman G. Underlying mechanisms of effective adoptive T cell therapy against a B cell lymphoma. [Doctoral Dissertation]. University of Melbourne; 2014. Available from: http://hdl.handle.net/11343/42223

University of Oxford
6.
Trenevska, Iva.
Developing anti-p53/HLA-A*0201 T-cell receptor mimic antibodies for cancer immunotherapy.
Degree: PhD, 2019, University of Oxford
URL: http://ora.ox.ac.uk/objects/uuid:7b2b8f73-4af0-40ef-bf2c-0e09cc194da6
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780790
► T-cell receptor mimic (TCRm) antibodies target a dual antigen epitope consisting of a peptide derived from an intracellular protein, and the major histocompatibility complex class…
(more)
▼ T-cell receptor mimic (TCRm) antibodies target a dual antigen epitope consisting of a peptide derived from an intracellular protein, and the major histocompatibility complex class I (MHC-I) molecule that presents the peptide at the cell surface. As traditional antibodies typically target cell surface or secreted antigens, TCRm antibodies advantageously expand the range of targetable antigens to include peptides derived from intracellular proteins. This thesis describes the development of TCRm antibodies targeting peptides that are derived from the wild type p53 protein and are presented by human leukocyte antigen (HLA)-A2. We further characterised the specificity and safety of the T1-116C TCRm antibody, which was the most extensively studied TCRm antibody in the laboratory prior to the start of this DPhil project. We showed that T1-116C labels primary AML and myeloma cells. We investigated the specificity of the T1-116C TCRm antibody for the p5365-73 peptide, RMPEAAPPV, by substituting each amino acid within the peptide individually, and showed that T1-116C recognises multiple tumour antigens. Using in silico analysis we identified 271 potentially cross-reactive peptides. We tested a panel of 25 peptides that are conserved in mice in vitro, showing that T1-116C binds peptides derived from a broad range of normal tissues. Despite these findings, in vivo testing of T1-116C cross-reactivity in human HLA-A2 transgenic mice demonstrated that T1-116C does not cause toxicity to normal mouse tissues. We also generated chimeric antigen receptors (CARs) for T-cell therapy using the single chain variable fragment of p53-targeting TCRm antibodies to provide the CAR specificity. We found that the CAR derived from T2-2A, a TCRm antibody that targets the p53187-197 peptide, GLAPPQHLIRV, demonstrated superior specificity for target peptide-HLA-A2 tetramers and cell lines to the T1-116C CAR. Through these studies, the T2-2A TCRm antibody has emerged as a potential therapeutic agent when used in the CAR format.
Subjects/Keywords: Cancer – Immunotherapy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Trenevska, I. (2019). Developing anti-p53/HLA-A*0201 T-cell receptor mimic antibodies for cancer immunotherapy. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:7b2b8f73-4af0-40ef-bf2c-0e09cc194da6 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780790
Chicago Manual of Style (16th Edition):
Trenevska, Iva. “Developing anti-p53/HLA-A*0201 T-cell receptor mimic antibodies for cancer immunotherapy.” 2019. Doctoral Dissertation, University of Oxford. Accessed March 05, 2021.
http://ora.ox.ac.uk/objects/uuid:7b2b8f73-4af0-40ef-bf2c-0e09cc194da6 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780790.
MLA Handbook (7th Edition):
Trenevska, Iva. “Developing anti-p53/HLA-A*0201 T-cell receptor mimic antibodies for cancer immunotherapy.” 2019. Web. 05 Mar 2021.
Vancouver:
Trenevska I. Developing anti-p53/HLA-A*0201 T-cell receptor mimic antibodies for cancer immunotherapy. [Internet] [Doctoral dissertation]. University of Oxford; 2019. [cited 2021 Mar 05].
Available from: http://ora.ox.ac.uk/objects/uuid:7b2b8f73-4af0-40ef-bf2c-0e09cc194da6 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780790.
Council of Science Editors:
Trenevska I. Developing anti-p53/HLA-A*0201 T-cell receptor mimic antibodies for cancer immunotherapy. [Doctoral Dissertation]. University of Oxford; 2019. Available from: http://ora.ox.ac.uk/objects/uuid:7b2b8f73-4af0-40ef-bf2c-0e09cc194da6 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780790
7.
Alderson, Kory L.
Deleterious Changes To The T Cell Compartment Following Immunotherapy.
Degree: 2009, University of Nevada – Reno
URL: http://hdl.handle.net/11714/4059
► Abstract: The combination of anti-CD40 and interleukin-2 is a potent immunotherapy regimen that results in synergistic anti-tumor responses. This has been demonstrated in multiple murine…
(more)
▼ Abstract: The combination of anti-CD40 and interleukin-2 is a potent
immunotherapy regimen that results in synergistic anti-tumor responses. This has been demonstrated in multiple murine tumor models of metastatic disease with various tumor types. The primary anti-tumor responses elicited by this combination are capable of inducing tumor regression and prolonged survival. However, the generation of secondary T cell responses after irradiated tumor vaccine is abrogated after anti-CD40 and IL-2. This abrogation also occurs after other immunotherapeutic approaches that prompt the production of large amounts of interferon-gamma (IFNγ). These observations correlated with a significant skewing of the T cell compartment. First, we observed a selective decreased of conventional CD4+ T cells following
immunotherapy. Second, we observed a more than five fold expansion of memory phenotype cells which were incapable of generating responses to new antigens. The data presented here suggest that despite initial tumor regression, potent systemic
immunotherapy may impair responses to new immunological challenges.Selective CD4+ T cell death after
immunotherapy results in an alteration in the ratio of CD4+ T cells to CD8+ T cells and impairs the generation of a secondary immune response. Our data suggest that this phenomenon after
immunotherapy is the result of the selective upregulation of programmed death-1 (PD-1) and its IFNγ responsive ligand, B7-H1. We show that the expression of PD-1 is restricted to the surface of Foxp3neg CD4+ T cells and that CD8+ T cells and CD4+ Foxp3+ regulatory T cells remain PD-1 low after
immunotherapy. Furthermore, the expression of PD-1 correlates with CD4+ T cell death after
immunotherapy. In the absence of IFNγ either by the use of mice lacking IFNγ (IFNγ-/-) or the receptor for IFNγ (IFNγR-/-), B7-H1 remains low after
immunotherapy. Subsequently, CD4+ T cells expand in response to
immunotherapy in the absence of IFNγ responsive B7-H1. We observed a significant expansion of memory phenotype T cells after cytokine based
immunotherapy which correlated with impairment of proliferative responses to new antigens. Memory T cells are more sensitive to cytokine stimulation than naïve T cells. Therefore, we used a young thymectomized mouse model to determine if pre-existing memory T cells were preferentially expanded by
immunotherapy. The thymectomized mouse model allowed us to evaluate long term T cell responses to
immunotherapy in the absence of de novo T cell generation. Using this model, we observed expansion of memory T cells, within both the CD4+ and CD8+ T cell compartments without a major sacrifice of the size of the naïve T cell compartment. Compared to memory T cell expansion, there was relatively small change in the naïve T cell compartment. Naïve CD8+ T cell numbers were unchanged by
immunotherapy and naïve CD4+ T cells were decreased by less than half. Memory T cells were still significantly expanded after 30 days of rest. Furthermore, the persistent…
Advisors/Committee Members: Murphy, William J. (advisor), Redelman, Doug (committee member), Hudig, Dorothy (committee member), Hunter, Kenneth (committee member), Wiltrout, Robert H. (committee member), Hogan, Mary Beth (committee member).
Subjects/Keywords: Immunotherapy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Alderson, K. L. (2009). Deleterious Changes To The T Cell Compartment Following Immunotherapy. (Thesis). University of Nevada – Reno. Retrieved from http://hdl.handle.net/11714/4059
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Alderson, Kory L. “Deleterious Changes To The T Cell Compartment Following Immunotherapy.” 2009. Thesis, University of Nevada – Reno. Accessed March 05, 2021.
http://hdl.handle.net/11714/4059.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Alderson, Kory L. “Deleterious Changes To The T Cell Compartment Following Immunotherapy.” 2009. Web. 05 Mar 2021.
Vancouver:
Alderson KL. Deleterious Changes To The T Cell Compartment Following Immunotherapy. [Internet] [Thesis]. University of Nevada – Reno; 2009. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/11714/4059.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Alderson KL. Deleterious Changes To The T Cell Compartment Following Immunotherapy. [Thesis]. University of Nevada – Reno; 2009. Available from: http://hdl.handle.net/11714/4059
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Rutgers University
8.
Newman, Jenna, 1993-.
Utilization of influenza vaccination as an intratumoral immunotherapy for cancer.
Degree: PhD, Microbiology and Molecular Genetics, 2019, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/61828/
► In recent years, immunotherapy for cancer has yielded unprecedented response rates and increased survival in patients. Despite progress, a significant fraction of patients exhibit progression…
(more)
▼ In recent years, immunotherapy for cancer has yielded unprecedented response rates and increased survival in patients. Despite progress, a significant fraction of patients exhibit progression of tumor growth during immunotherapy treatment. One barrier to response is the tumor microenvironment; patients who lack immune infiltration of their tumors or exhibit infiltration of suppressive cell subsets often do not respond to immunotherapy. In an effort to infiltrate the tumor microenvironment with pro-inflammatory cells (such as CD8+ T cells) that are correlated with response to immunotherapy in the clinic, inactivated influenza was administered intratumorally in immunocompetent mice. This vaccination slowed tumor growth when compared to that of mock-treated controls, and yielded an increased proportion in the tumor of dendritic cells, cross-presenting dendritic cells, CD8+ T cells, and tumor-reactive CD8+ T cells –all critical for anti-tumor immunity. Moreover, analysis of RNA from the vaccinated tumor revealed an upregulation in transcripts indicative of an inflamed tumor microenvironment, relative to that observed in mock-treated controls. Intratumoral influenza vaccination administered in combination with checkpoint blockade (αPD-L1) immunotherapy resulted in superior tumor control relative to that observed with either therapy alone. Further benefit derived from the intratumoral vaccination was protection from influenza infection. Interestingly, one vaccine formulation tested contained a squalene-based adjuvant; this vaccine did not slow tumor growth and failed to reduce the proportion of suppressive B regulatory cells (Bregs) in the tumor. Depletion of Bregs enabled the adjuvanted influenza vaccine to slow tumor growth. The research discussed in this dissertation indicates that intratumoral influenza vaccination may be used in the future as an immunotherapy for cancer; clinical trials are currently in preparation.
Advisors/Committee Members: Denzin, Lisa (chair), Rabson, Arnold (internal member), Covey, Lori (outside member), School of Graduate Studies.
Subjects/Keywords: Cancer – Immunotherapy
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Newman, Jenna, 1. (2019). Utilization of influenza vaccination as an intratumoral immunotherapy for cancer. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/61828/
Chicago Manual of Style (16th Edition):
Newman, Jenna, 1993-. “Utilization of influenza vaccination as an intratumoral immunotherapy for cancer.” 2019. Doctoral Dissertation, Rutgers University. Accessed March 05, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/61828/.
MLA Handbook (7th Edition):
Newman, Jenna, 1993-. “Utilization of influenza vaccination as an intratumoral immunotherapy for cancer.” 2019. Web. 05 Mar 2021.
Vancouver:
Newman, Jenna 1. Utilization of influenza vaccination as an intratumoral immunotherapy for cancer. [Internet] [Doctoral dissertation]. Rutgers University; 2019. [cited 2021 Mar 05].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/61828/.
Council of Science Editors:
Newman, Jenna 1. Utilization of influenza vaccination as an intratumoral immunotherapy for cancer. [Doctoral Dissertation]. Rutgers University; 2019. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/61828/
9.
Jirakrit Saetang.
Anti-cancer Immunologic Function of Recombinant Interleukin-18
.
Degree: คณะแพทยศาสตร์ ภาควิชาชีวเวชศาสตร์, 2018, Prince of Songkla University
URL: http://kb.psu.ac.th/psukb/handle/2016/12534
Subjects/Keywords: Immunotherapy;
Cancer Immunotherapy
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Saetang, J. (2018). Anti-cancer Immunologic Function of Recombinant Interleukin-18
. (Thesis). Prince of Songkla University. Retrieved from http://kb.psu.ac.th/psukb/handle/2016/12534
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Saetang, Jirakrit. “Anti-cancer Immunologic Function of Recombinant Interleukin-18
.” 2018. Thesis, Prince of Songkla University. Accessed March 05, 2021.
http://kb.psu.ac.th/psukb/handle/2016/12534.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Saetang, Jirakrit. “Anti-cancer Immunologic Function of Recombinant Interleukin-18
.” 2018. Web. 05 Mar 2021.
Vancouver:
Saetang J. Anti-cancer Immunologic Function of Recombinant Interleukin-18
. [Internet] [Thesis]. Prince of Songkla University; 2018. [cited 2021 Mar 05].
Available from: http://kb.psu.ac.th/psukb/handle/2016/12534.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Saetang J. Anti-cancer Immunologic Function of Recombinant Interleukin-18
. [Thesis]. Prince of Songkla University; 2018. Available from: http://kb.psu.ac.th/psukb/handle/2016/12534
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
10.
Little, Nicole S.
Investigating the co-evolution of tumor antigens and the anti-tumor immune response.
Degree: Department of Biochemistry and Microbiology, 2017, University of Victoria
URL: https://dspace.library.uvic.ca//handle/1828/8503
► Background: High-grade serous carcinoma (HGSC) can exhibit high intratumoral heterogeneity (ITH). Despite a strong association between tumor-infiltrating lymphocytes (TIL) and survival in HGSC, ITH may…
(more)
▼ Background: High-grade serous carcinoma (HGSC) can exhibit high intratumoral heterogeneity (ITH). Despite a strong association between tumor-infiltrating lymphocytes (TIL) and survival in HGSC, ITH may have profound impacts on the anti-tumor T cell response. Yet, it is unknown how anti-tumor T cell responses contend with ITH over time in HGSC. Previous studies in melanoma and HGSC both showed tumor-reactive T cell clones emerge over time with their cognate tumor-antigens. Therefore, I hypothesized patients would share a common mechanism of T cell evolution to respond to ITH in HGSC. If so, I expect to see similar patterns of tumor recognition between primary and recurrent disease.
Methods: Tumor-associated lymphocytes (TAL) were expanded from primary and recurrent ascites samples using high-dose IL-2 and a rapid-expansion protocol (REP). Following expansion, TAL were assessed for recognition of autologous tumor by IFN-γ ELISPOT and flow cytometry for CD137. CD137+ tumor-reactive TAL were FACS-purified and the tumor-reactive T cell repertoire was profiled by deep sequencing of TCRβ chains (TCRseq). Tumor-reactive TCR clonotypes were compared between primary and recurrent disease to elucidate differences in tumor-reactive populations over time in HGSC.
Results: Patient TAL recognized tumor in two out of three cases. In patient IROC 060, the tumor became more immunogenic between primary and recurrent disease, which may reflect expression of new antigens and/or loss of an immunosuppressive phenotype. In patient IROC 106, the tumor remained immunogenic between primary and recurrent disease, which may reflect maintenance of stable antigen expression and an immune-sensitive phenotype. Patient IROC 034 did not exhibit any tumor-reactivity, suggesting tumor-reactivity is not ubiquitous in HGSC. FACS-purification of CD137+ T cells followed by TCRseq was successfully performed on T cell populations of both high- and low-abundance, suggesting TCRseq can be performed on populations containing very few T cells. TCRseq results that profiled the clonal repertoire of tumor-reactive TAL from primary and recurrent disease in two patients, IROC 060 and IROC 106, showed both patients had evidence of T cell loss and T cell emergence between primary and recurrent disease. Further, IROC 106 had evidence of T cell clones that were maintained between primary and recurrent disease.
Conclusions: Anti-tumor T cell responses from ascites are both diverse between patients and dynamic within a patient, suggesting various mechanisms of T cell evolution to contend with ITH in HGSC. I developed a pipeline for the identification of tumor-reactive TCR sequences without the need for a priori knowledge of specific antigens. Additionally, this pipeline is feasible for very low-abundance samples, such as tumor-reactive T cells.
Significance: This study provides early insights into how TAL contend with ITH in HGSC. Ultimately, these results will inform the design of adoptive T cell therapy for recurrent HGSC.
Advisors/Committee Members: Nelson, Brad H. (supervisor).
Subjects/Keywords: Cancer; Cancer Immunotherapy; Ovarian Cancer; Immunology; Immunotherapy
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Little, N. S. (2017). Investigating the co-evolution of tumor antigens and the anti-tumor immune response. (Masters Thesis). University of Victoria. Retrieved from https://dspace.library.uvic.ca//handle/1828/8503
Chicago Manual of Style (16th Edition):
Little, Nicole S. “Investigating the co-evolution of tumor antigens and the anti-tumor immune response.” 2017. Masters Thesis, University of Victoria. Accessed March 05, 2021.
https://dspace.library.uvic.ca//handle/1828/8503.
MLA Handbook (7th Edition):
Little, Nicole S. “Investigating the co-evolution of tumor antigens and the anti-tumor immune response.” 2017. Web. 05 Mar 2021.
Vancouver:
Little NS. Investigating the co-evolution of tumor antigens and the anti-tumor immune response. [Internet] [Masters thesis]. University of Victoria; 2017. [cited 2021 Mar 05].
Available from: https://dspace.library.uvic.ca//handle/1828/8503.
Council of Science Editors:
Little NS. Investigating the co-evolution of tumor antigens and the anti-tumor immune response. [Masters Thesis]. University of Victoria; 2017. Available from: https://dspace.library.uvic.ca//handle/1828/8503

Victoria University of Wellington
11.
Hunn, Martin Kent.
Improving immunotherapy for high grade glioma.
Degree: 2015, Victoria University of Wellington
URL: http://hdl.handle.net/10063/4869
► Glioblastoma multiforme (GBM) is a malignant primary brain tumour that is almost always fatal. Conventional treatment modalities are limited by toxicity. T cell-based immunotherapy is…
(more)
▼ Glioblastoma multiforme (GBM) is a malignant primary brain tumour that is almost always fatal. Conventional treatment modalities are limited by toxicity. T cell-based
immunotherapy is a promising alternative that has the potential to specifically target tumour cells.
The author of this thesis was a principal investigator for a recently completed Phase I clinical trial in which patients with recurrent GBM were treated with surgery, dendritic cell-based
immunotherapy and chemotherapy. In addition to conducting the trial in collaboration with others, the author used peripheral blood mononuclear cells from trial participants to assess anti-tumour immune responses before and after treatment. A broad correlation was observed between clinical outcome and anti-tumour immunity, with sustained progression-free survival occurring in two patients with baseline responses that persisted or increased after treatment. However, the overall clinical benefit was modest. For progress to be made, there is a need to develop a more potent vaccine.
With this in mind, a novel “Glioma-Gal” vaccine was devised and tested in an orthotopic mouse model of glioma, This simple vaccine consisted of irradiated autologous tumour cells pulsed with the glycolipid alpha-galactosylceramide, an immunoadjuvant that induces invariant Natural Killer T cells to licence endogenous dendritic cells. The vaccine was shown to be effective in a therapeutic setting when accompanied by depletion of regulatory T cells. Mechanistically, vaccine efficacy was dependent on CD4 T cells and the mediastinal lymph node was shown to be an important site of T cell priming. It was further shown that components of the immune system necessary for the vaccine to work were present and competent in a cohort of GBM patients.
The final chapters explore the idea of enhancing the therapeutic benefit of this vaccine by targeting certain tumour cell subsets or phenotypes. Cancer stem cells (CSC) are proposed to be a subset of tumour cells with a unique capacity for initiating and maintaining tumours. Eliminating these cells may therefore be both necessary and sufficient to achieve cure. Using the same mouse model, a variety of methods were assessed for their ability to isolate or enrich for a CSC subset. Of these, culture in serum-free medium in the presence of certain growth factors was shown to enrich for a more stem cell-like phenotype. However, a vaccine constructed from these stem cell-like cells was not more effective than the standard vaccine. Next, the author tested the hypothesis that a vaccine manipulated to target chemoresistant cells would be more effective than standard vaccine when used in combination with chemotherapy. However, the modified vaccine showed no advantage over standard vaccine in this model. In the course of these experiments, synergy was observed between the vaccine and the chemotherapy agent doxorubicin. The mechanism responsible for this supra-additive effect remains undetermined but is most likely due to an immunomodulatory effect of low dose doxorubicin.…
Advisors/Committee Members: Hermans, Ian.
Subjects/Keywords: Glioma; Immunotherapy; Vaccine
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hunn, M. K. (2015). Improving immunotherapy for high grade glioma. (Doctoral Dissertation). Victoria University of Wellington. Retrieved from http://hdl.handle.net/10063/4869
Chicago Manual of Style (16th Edition):
Hunn, Martin Kent. “Improving immunotherapy for high grade glioma.” 2015. Doctoral Dissertation, Victoria University of Wellington. Accessed March 05, 2021.
http://hdl.handle.net/10063/4869.
MLA Handbook (7th Edition):
Hunn, Martin Kent. “Improving immunotherapy for high grade glioma.” 2015. Web. 05 Mar 2021.
Vancouver:
Hunn MK. Improving immunotherapy for high grade glioma. [Internet] [Doctoral dissertation]. Victoria University of Wellington; 2015. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/10063/4869.
Council of Science Editors:
Hunn MK. Improving immunotherapy for high grade glioma. [Doctoral Dissertation]. Victoria University of Wellington; 2015. Available from: http://hdl.handle.net/10063/4869

University of Otago
12.
Bouwer, Anthea Lynne.
Role of NK cells in DC-based immunotherapy of melanoma
.
Degree: 2011, University of Otago
URL: http://hdl.handle.net/10523/1619
► Natural killer (NK) cells were first identified by their ability to kill tumour or virally infected cells without prior sensitization. In spite of this, the…
(more)
▼ Natural killer (NK) cells were first identified by their ability to kill tumour or virally infected cells without prior sensitization. In spite of this, the actual role of NK cells in tumour
immunotherapy remains controversial. This study therefore set out to investigate the potential of Streptococcus salivarius K12, a gram-positive bacterium that has a history of commercial application as a probiotic in New Zealand, for use as a NK cell adjuvant, applying the therapy using B16.OVA melanoma as a model. To confirm that S. salivarius K12 was able to induce efficient activation of NK cells, I first screened a number of gram-positive and gram-negative bacteria for their ability to induce IFNγ release from NK cells. Using ELISA and fluorescence activated cell sorting (FACS) I found that gram-positive bacteria stimulated a rapid release (<24 hours) of IFNγ from dendritic cell: NK cell co-cultures. Cytotoxicity assays showed that despite optimal activation of NK cells by S. salivarius K12, their cytotoxic activity was not enhanced above that of the naive NK cells. Dissecting NK cells into two subsets based on their CD27 expression using FACS, it was discovered that S. salivarius K12-NK activation was predominantly exerted on the mature CD27high NK cell subset and was dependent on membrane-contact with DC and IL-12/IL-18 expression. NK cell activation was found to be independent of Ly49A expression, a marker that can be used in C57BL/6 mice to discriminate between 'unlicensed' NK cells, and those that had been 'licensed' through interaction with self MHC during development. Therefore having a setting where the addition of S. salivarius K12 activates NK cells, I investigated whether these NK cells were recruited to the draining lymph nodes where they could potentially influence the adaptive immune response. A range of adjuvant-activated and S. salivarius K12-activated DC were injected subcutaneously into the flanks of mice and tested their ability to recruit NK cells to the draining lymph node. The adjuvants differed markedly in their ability to recruit NK cells with S. salivarius K12 being the most effective. To determine if activated NK cells would be of benefit in tumour
immunotherapy, I investigated the ability of bacterially activated DCs to elicit anti-tumour responses in a B16.OVA melanoma model. Utilizing a therapeutic tumour model where treatment was started three days following tumour inoculation, I found a significant delay of tumour growth in mice that were immunized with ovalbumin-pulsed DC that had been treated for 4 hours with S. salivarius K12 as opposed to other adjuvants tested. I also determined that in vivo depletion of NK cells completely abolished the benefit of DC
immunotherapy. A therapeutic tumour experiment where DC were primed in the presence or absence of tumour antigen showed that while NK cells were critical for the antigen-dependent anti-tumour response they did not appear to exert an effector function. To investigate the role of NK cells in priming the anti-tumour response I next utilized a…
Advisors/Committee Members: McLellan, Alexander Donald (advisor).
Subjects/Keywords: NK cells;
immunotherapy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bouwer, A. L. (2011). Role of NK cells in DC-based immunotherapy of melanoma
. (Doctoral Dissertation). University of Otago. Retrieved from http://hdl.handle.net/10523/1619
Chicago Manual of Style (16th Edition):
Bouwer, Anthea Lynne. “Role of NK cells in DC-based immunotherapy of melanoma
.” 2011. Doctoral Dissertation, University of Otago. Accessed March 05, 2021.
http://hdl.handle.net/10523/1619.
MLA Handbook (7th Edition):
Bouwer, Anthea Lynne. “Role of NK cells in DC-based immunotherapy of melanoma
.” 2011. Web. 05 Mar 2021.
Vancouver:
Bouwer AL. Role of NK cells in DC-based immunotherapy of melanoma
. [Internet] [Doctoral dissertation]. University of Otago; 2011. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/10523/1619.
Council of Science Editors:
Bouwer AL. Role of NK cells in DC-based immunotherapy of melanoma
. [Doctoral Dissertation]. University of Otago; 2011. Available from: http://hdl.handle.net/10523/1619

McMaster University
13.
Rathmann, Stephanie.
Development of a Versatile Platform for Combination Targeted Radionuclide and Immune Cell Recruitment Therapies using Bio-orthogonal Chemistry.
Degree: PhD, 2020, McMaster University
URL: http://hdl.handle.net/11375/25928
► This thesis describes a general platform for the synthesis of radiolabelled antibody recruiting small molecules (R-ARMs) for combination radio and immune recruitment therapies. The novel…
(more)
▼ This thesis describes a general platform for the synthesis of radiolabelled antibody recruiting small molecules (R-ARMs) for combination radio and immune recruitment therapies. The novel trifunctional ARM was synthesized and radiolabelled with beta (lutetium-177) and alpha (actinium-225) emitting radionuclides in high yield. Biodistribution of the lutetium-ARM revealed rapid renal clearance and minimal uptake in non-target tissues with all organs and tissues containing less than 0.3 %ID/g by 24 hours post-injection. Having determined the pharmacokinetic properties of the ligand, a biodistribution study was performed to determine the targeting potential of the platform. Through the use of a validated bone targeted bisphosphonate, uptake in the arm and leg bones was achieved. Flow cytometry studies successfully demonstrated ARM and antibody dependent immune cell recruitment. Based on the promising results of the ARM in vitro and in vivo, the next step was to perform therapy studies.
In order to validate the novel R-ARM, an intratumoral (i.t.) strategy was developed through the preparation of a TCO-bovine serum albumin (BSA) derivative. This new chemical entity was used in both an aggregated and non-aggregated form to retain the R-ARM in the tumour after i.t. administration. Biodistribution showed high retention of the aggregated and non-aggregated BSA out to 120 hours with 167 ± 94 and 81 ± 32 %ID/g respectively remaining in the tumour. An autoradiography study revealed the after i.t. administration the aggregated material was localized in specific regions within the tumour compared to the non-aggregated material which diffused throughout. The aggregated material was used in a single and multi-dosing radiotherapy study in which the latter induced a statistically significant survival advantage compared to the control. One additional multi-dosing study was performed with the non-
aggregated material which resulted in the largest survival advantage to date. Intratumoral administration of TCO-BSA linked to the trifunctional tetrazine showed promising radiotherapy results and future work on dose optimization with lutetium and actinium is required prior to the combination R-ARM therapy.
In parallel, the efficacy of the unlabelled ARM linked to TCO-BSA was interrogated in preclinical models. The compound was administered i.t. three times per week in a breast cancer tumour model, and response to therapy monitored. The immunized group showed no survival advantage compared to the control group comprised of naïve animals. Biodistribution studies were performed to determine if TCO-BSA was accessible to the bloodstream following i.t. administration in both the aggregated and non-aggregated forms. Saline, aggregated or non-aggregated TCO-BSA were administered i.t. followed by the R-ARM. The results showed very low uptake in the tumour for all three groups, with minimal change in distribution from that of the native R-ARM. This suggests that after i.t. administration, the TCO-BSA was not available to molecules in the bloodstream…
Advisors/Committee Members: Valliant, John, Chemistry.
Subjects/Keywords: Cancer; Immunotherapy; Radiotherapy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Rathmann, S. (2020). Development of a Versatile Platform for Combination Targeted Radionuclide and Immune Cell Recruitment Therapies using Bio-orthogonal Chemistry. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/25928
Chicago Manual of Style (16th Edition):
Rathmann, Stephanie. “Development of a Versatile Platform for Combination Targeted Radionuclide and Immune Cell Recruitment Therapies using Bio-orthogonal Chemistry.” 2020. Doctoral Dissertation, McMaster University. Accessed March 05, 2021.
http://hdl.handle.net/11375/25928.
MLA Handbook (7th Edition):
Rathmann, Stephanie. “Development of a Versatile Platform for Combination Targeted Radionuclide and Immune Cell Recruitment Therapies using Bio-orthogonal Chemistry.” 2020. Web. 05 Mar 2021.
Vancouver:
Rathmann S. Development of a Versatile Platform for Combination Targeted Radionuclide and Immune Cell Recruitment Therapies using Bio-orthogonal Chemistry. [Internet] [Doctoral dissertation]. McMaster University; 2020. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/11375/25928.
Council of Science Editors:
Rathmann S. Development of a Versatile Platform for Combination Targeted Radionuclide and Immune Cell Recruitment Therapies using Bio-orthogonal Chemistry. [Doctoral Dissertation]. McMaster University; 2020. Available from: http://hdl.handle.net/11375/25928

Victoria University of Wellington
14.
Bilbrough, Timothy.
Designing distribution of adjuvants: Synthesis of lipidated nucleic acid adjuvant compounds.
Degree: 2017, Victoria University of Wellington
URL: http://hdl.handle.net/10063/9097
► Peptide vaccines can generate antigen-specific immune responses against tumours. However, peptides on their own are not usually immunogenic and require an adjuvant to ensure antigen-presenting…
(more)
▼ Peptide vaccines can generate antigen-specific immune responses against tumours. However, peptides on their own are not usually immunogenic and require an adjuvant to ensure antigen-presenting cells are appropriately activated. Adjuvant localisation is essential for its activity; targeting an immunomodulatory compound to the lymph nodes appropriately positions it among a high density of immune cells, where immune responses are coordinated. Furthermore, systemic distribution of a potent immune modulator can lead to severe systemic toxicities. Lymph node targeting reduces systemic exposure with simultaneous reduction of side effects. Where a compound distributes in viva is determined by its pharmacokinetic properties and its route of administration. Once the route has been defined, a drug's pharmacokinetic properties can be modified by structural changes. To this end, we modified existing adjuvants to distribute into the lymphatics preferentially. One method was to increase the hydrophilicity and size of agalactosylceramide to favour lymphatic uptake. The second was to exploit albumin hitchhiking to access the lymph nodes. Here, a-galactosylceramide was chemically linked via an enzyme-labile linker to CpG ODN 1826, a TLR-9 agonist. The properties of each adjuvant mutually alter those of the other: to the CpG, a-galactosylceramide acts as an albumin binding domain; to the a-galactosylceramide, the CpG serves as a large hydrophilic group creating an amphiphile. In vivo, this should activate a strong, multilineage T cell response through the synergy of the two adjuvants. Furthermore, this should reduce the toxicity and side effects of the adjuvant by limiting its systemic distribution. This adjuvant may find further use in vaccines for diseases requiring a Thl response for effective clearance.
Advisors/Committee Members: Painter, Gavin, Anderson, Regan.
Subjects/Keywords: Immunotherapy; Adjuvant; Glycolipid
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bilbrough, T. (2017). Designing distribution of adjuvants: Synthesis of lipidated nucleic acid adjuvant compounds. (Masters Thesis). Victoria University of Wellington. Retrieved from http://hdl.handle.net/10063/9097
Chicago Manual of Style (16th Edition):
Bilbrough, Timothy. “Designing distribution of adjuvants: Synthesis of lipidated nucleic acid adjuvant compounds.” 2017. Masters Thesis, Victoria University of Wellington. Accessed March 05, 2021.
http://hdl.handle.net/10063/9097.
MLA Handbook (7th Edition):
Bilbrough, Timothy. “Designing distribution of adjuvants: Synthesis of lipidated nucleic acid adjuvant compounds.” 2017. Web. 05 Mar 2021.
Vancouver:
Bilbrough T. Designing distribution of adjuvants: Synthesis of lipidated nucleic acid adjuvant compounds. [Internet] [Masters thesis]. Victoria University of Wellington; 2017. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/10063/9097.
Council of Science Editors:
Bilbrough T. Designing distribution of adjuvants: Synthesis of lipidated nucleic acid adjuvant compounds. [Masters Thesis]. Victoria University of Wellington; 2017. Available from: http://hdl.handle.net/10063/9097

University of Otago
15.
Win, Stephanie Joy.
Inducing Anti-Tumor Immune Responses with Antigen Conjugated Virus-Like Particles
.
Degree: 2011, University of Otago
URL: http://hdl.handle.net/10523/1733
► Virus-like particles (VLP) have been shown to be useful nanoscale platforms in a diverse range of applications including their use as vaccines. They can act…
(more)
▼ Virus-like particles (VLP) have been shown to be useful nanoscale platforms in a diverse range of applications including their use as vaccines. They can act as vehicles for the delivery of heterologous antigens to the immune system thereby initiating strong anti-tumor responses. Model tumor antigens chemically coupled to rabbit hemorrhagic disease virus VLP (RHDV VLP) have been shown to delay or prevent the development of tumors in vivo using an aggressive model of murine melanoma. RHDV VLP are amenable to conjugation with a range of peptide antigens, single proteins or complex tumor lysates, all of which are relevant for studying immune responses to tumors in mouse models or with human systems in vitro.
Dendritic cells (DC) play a key role in the development of anti-tumor T cell responses due to their ability to take up antigens, process them into peptides and present them to CD8+ T cells on MHC-I by cross-presentation. Inhibitor studies showed RHDV VLP are rapidly taken up by both mouse- and human-derived DC by macropinocytosis and phagocytosis and are subsequently prepared for presentation on MHC-I that has recycled from the cell surface within acidified lysosomal compartments. Additionally, the ability of murine DC to cross-present VLP does not seem to be confined to specific subsets as DC expressing CD8α were able to cross-present VLP-SIINFEKL in vivo, to equivalent levels as other populations of DC.
RHDV VLP conjugated to tumor peptides or lysates do not stimulate phenotypic maturation of the DC required for the cross-priming of naïve T cell responses. The addition of an adjuvant, either OK432 or oncolytic reovirus, to DC pulsed with VLP-MART1 or VLP-Lysates, resulted in phenotypic maturation of DC and enabled the priming of naïve T cells able to produce IFN-γ and directly lyse specific target cells. Furthermore, MART-1 specific MHC-I pentamer staining demonstrated the expansion of CD8+ T cells possessing a TCR specific for MART-1 while the T cells took on a more activated, effector memory phenotype through diminished expression of CD45RA and increased expression of CD45RO and CCR7. Importantly, T cell responses primed using VLP-MART1 or VLP-Lysate with either adjuvant were more pronounced than where MART1 peptide or Lysate was used with that same adjuvant indicating a significant benefit in delivery of antigen on VLP. Collectively, these results indicate that VLP-conjugates, together with adjuvant, have the ability to stimulate cytotoxic T cell responses specifically against tumor cells.
Production of a VLP able to induce DC maturation was attempted by conjugation of melanoma lysates infected previously with oncolytic reovirus to the VLP (VLP-ReoLysate). Results indicate that these VLP-ReoLysate are able to induce activation of innate NK and NKT cells as well as DC. Furthermore, DC pulsed with VLP-ReoLysate resulted in priming of naïve T cells with cytotoxic capabilities against melanoma cells in vitro, however minimal differences were seen where ReoLysates were delivered alone or conjugated to…
Advisors/Committee Members: Baird, Margaret (advisor).
Subjects/Keywords: Virus-Like Particles;
Immunotherapy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Win, S. J. (2011). Inducing Anti-Tumor Immune Responses with Antigen Conjugated Virus-Like Particles
. (Doctoral Dissertation). University of Otago. Retrieved from http://hdl.handle.net/10523/1733
Chicago Manual of Style (16th Edition):
Win, Stephanie Joy. “Inducing Anti-Tumor Immune Responses with Antigen Conjugated Virus-Like Particles
.” 2011. Doctoral Dissertation, University of Otago. Accessed March 05, 2021.
http://hdl.handle.net/10523/1733.
MLA Handbook (7th Edition):
Win, Stephanie Joy. “Inducing Anti-Tumor Immune Responses with Antigen Conjugated Virus-Like Particles
.” 2011. Web. 05 Mar 2021.
Vancouver:
Win SJ. Inducing Anti-Tumor Immune Responses with Antigen Conjugated Virus-Like Particles
. [Internet] [Doctoral dissertation]. University of Otago; 2011. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/10523/1733.
Council of Science Editors:
Win SJ. Inducing Anti-Tumor Immune Responses with Antigen Conjugated Virus-Like Particles
. [Doctoral Dissertation]. University of Otago; 2011. Available from: http://hdl.handle.net/10523/1733
16.
Hu, Hong-Ming.
Priming of therapeutic T cells for adoptive immunotherapy.
Degree: PhD, 2003, Oregon Health Sciences University
URL: doi:10.6083/M4HX19ZF
;
http://digitalcommons.ohsu.edu/etd/3146
Subjects/Keywords: Immunotherapy; Adoptive
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hu, H. (2003). Priming of therapeutic T cells for adoptive immunotherapy. (Doctoral Dissertation). Oregon Health Sciences University. Retrieved from doi:10.6083/M4HX19ZF ; http://digitalcommons.ohsu.edu/etd/3146
Chicago Manual of Style (16th Edition):
Hu, Hong-Ming. “Priming of therapeutic T cells for adoptive immunotherapy.” 2003. Doctoral Dissertation, Oregon Health Sciences University. Accessed March 05, 2021.
doi:10.6083/M4HX19ZF ; http://digitalcommons.ohsu.edu/etd/3146.
MLA Handbook (7th Edition):
Hu, Hong-Ming. “Priming of therapeutic T cells for adoptive immunotherapy.” 2003. Web. 05 Mar 2021.
Vancouver:
Hu H. Priming of therapeutic T cells for adoptive immunotherapy. [Internet] [Doctoral dissertation]. Oregon Health Sciences University; 2003. [cited 2021 Mar 05].
Available from: doi:10.6083/M4HX19ZF ; http://digitalcommons.ohsu.edu/etd/3146.
Council of Science Editors:
Hu H. Priming of therapeutic T cells for adoptive immunotherapy. [Doctoral Dissertation]. Oregon Health Sciences University; 2003. Available from: doi:10.6083/M4HX19ZF ; http://digitalcommons.ohsu.edu/etd/3146

Cornell University
17.
Chandrasekaran, Siddarth.
Engineering Approaches To Analyze And Target Cancer Invasion And Metastasis.
Degree: PhD, Biomedical Engineering, 2015, Cornell University
URL: http://hdl.handle.net/1813/41158
► Metastasis of primary tumor accounts for 90% of all deaths in cancer patients. Interaction between cells in the primary tumor is known to play an…
(more)
▼ Metastasis of primary tumor accounts for 90% of all deaths in cancer patients. Interaction between cells in the primary tumor is known to play an important role in determining the metastatic potential of cancer cells that leave the primary site. Cancer cells that metastasize through the bloodstream invade through the basement membrane surrounding the primary tumor to enter the adjacent blood capillaries. Then, they can evade the host immune response in the circulation and interact with E-selectin on endothelial cells lining the blood vessel wall to exit the circulation and establish at a secondary site. The first focus of my project was to study the effect of homotypic and heterotypic cell-cell interactions on the metastatic potential of cancer cells using a 3D tumor spheroid model. 3D spheroids generated by culturing breast cancer cell lines on polydimethylsiloxane had stronger interaction with E-selectin, increased invasiveness and resistance to apoptosis inducing signals in the circulation when compared to their respective 2D monolayer grown counterparts on tissue culture plate. Cancer cells entering the lymphatic system get lodged within the tumor draining lymph nodes (TDLN), thus contributing to the lymphatic spread of cancer. Natural killer (NK) cells in the TDLN elicit an anti-tumor response by expressing Tumor necrosis factor-[alpha] Related Apoptosis Inducing Ligand (TRAIL) on their surface. TRAIL can bind to death receptors on cancer cells and induce apoptosis. Despite the presence of immunoregulatory NK cells, lymph node metastases are prevalent in several types of cancers. This is because of the abnormalities of NK cells in the TDLN, including reduced count and decreased cytotoxicity. Given the coexistence of cancer cells and NK cells within the TDLN, the second part of this dissertation was focused on demonstrating a nanomedicine-based approach to enhance the therapeutic efficacy of endogenous NK cells by coating them with liposomes functionalized with TRAIL. Human NK cells coated with TRAIL liposomes were able to induce apoptosis in cancer cells cultured in engineered lymph node microenvironments. Liposomes functionalized with TRAIL and an antibody against mouse NK cells were carried to the TDLN and prevented the lymphatic spread of a subcutaneous tumor in mice.
Advisors/Committee Members: King,Michael R. (chair), Shen,Xiling (committee member), Putnam,David A. (committee member).
Subjects/Keywords: Cancer Metastasis; Drug Delivery; Immunotherapy
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Chandrasekaran, S. (2015). Engineering Approaches To Analyze And Target Cancer Invasion And Metastasis. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/41158
Chicago Manual of Style (16th Edition):
Chandrasekaran, Siddarth. “Engineering Approaches To Analyze And Target Cancer Invasion And Metastasis.” 2015. Doctoral Dissertation, Cornell University. Accessed March 05, 2021.
http://hdl.handle.net/1813/41158.
MLA Handbook (7th Edition):
Chandrasekaran, Siddarth. “Engineering Approaches To Analyze And Target Cancer Invasion And Metastasis.” 2015. Web. 05 Mar 2021.
Vancouver:
Chandrasekaran S. Engineering Approaches To Analyze And Target Cancer Invasion And Metastasis. [Internet] [Doctoral dissertation]. Cornell University; 2015. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/1813/41158.
Council of Science Editors:
Chandrasekaran S. Engineering Approaches To Analyze And Target Cancer Invasion And Metastasis. [Doctoral Dissertation]. Cornell University; 2015. Available from: http://hdl.handle.net/1813/41158

Vanderbilt University
18.
Dockery, Mary Diana.
Focused Ultrasound for the Generation of Cancer Immunotherapy.
Degree: MS, Biomedical Engineering, 2016, Vanderbilt University
URL: http://hdl.handle.net/1803/14703
► Cancer immunotherapies, which seek to arm the patient’s own immune system for personalized therapy, are a promising option for effective elimination of tumors. Focused ultrasound…
(more)
▼ Cancer immunotherapies, which seek to arm the patient’s own immune system for personalized therapy, are a promising option for effective elimination of tumors. Focused ultrasound (FUS) is one propitious method for generating anti-tumor
immunotherapy, advantageous in its capacity to deliver non-ionizing, non-invasive, tumor-localized treatment; this involves the transdermal deposition of sonic energy at a focal point in the tumor, which induces acute inflammation capable of activating an anti-tumor immune response. Here, we characterize,
in vivo, the early (48 hours) adaptive anti-tumor immune responses induced by FUS treatment of tumors. Compared to untreated tumors, tumors treated with mechanical FUS (mFUS) demonstrated increased NF-κB activation in local and distant tumors. Additionally, a “responder” subset of mFUS-treated mice was identified and mFUS-treated tumors exhibited an increased percent of CD4+ T cells and an increased CD4+/CD8+ T cell ratio, as compared to untreated tumors. Immunohistochemical analysis of CD4+ T cells revealed a higher presence of immunostimulatory phenotypes in mFUS-treated tumors compared to untreated tumors. Taken together, these results suggested a FUS-induced shift towards anti-tumor immune activity.
Advisors/Committee Members: Charles F Caskey (committee member), Todd D Giorgio (Committee Chair).
Subjects/Keywords: immunotherapy; focused ultrasound; breast cancer
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Dockery, M. D. (2016). Focused Ultrasound for the Generation of Cancer Immunotherapy. (Thesis). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14703
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Dockery, Mary Diana. “Focused Ultrasound for the Generation of Cancer Immunotherapy.” 2016. Thesis, Vanderbilt University. Accessed March 05, 2021.
http://hdl.handle.net/1803/14703.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Dockery, Mary Diana. “Focused Ultrasound for the Generation of Cancer Immunotherapy.” 2016. Web. 05 Mar 2021.
Vancouver:
Dockery MD. Focused Ultrasound for the Generation of Cancer Immunotherapy. [Internet] [Thesis]. Vanderbilt University; 2016. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/1803/14703.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Dockery MD. Focused Ultrasound for the Generation of Cancer Immunotherapy. [Thesis]. Vanderbilt University; 2016. Available from: http://hdl.handle.net/1803/14703
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Vanderbilt University
19.
Bright, Vanessa Rochelle.
Multimodal nanoparticles for cancer therapy and imaging.
Degree: MS, Chemical and Physical Biology, 2012, Vanderbilt University
URL: http://hdl.handle.net/1803/14622
► In this thesis, the power of synthetic chemistry and colloidal nanotechnology are employed in the advancement of cell therapy and imaging. A new approach to…
(more)
▼ In this thesis, the power of synthetic chemistry and colloidal nanotechnology are employed in the advancement of cell therapy and imaging. A new approach to dendritic cell (DC)-based
immunotherapy is examined with the use of a MUC1 tumor mouse, and the utilization of superparamagnetic iron oxide (SPIO) nanoparticles as delivery vehicles is also explored. The nanoparticle is conjugated to MUC1 tumor antigen and α-GalCer, an innate immune adjuvant. Preliminary data of the efficacy of this therapy are presented, thus promoting further research in this area. This multimodal nanovaccine enables activation of DCs endogenously. Nebulization is examined as a means of delivering the nanovaccine to the DC-rich tissues of the lungs. Results of staining and imaging of the lungs and lymph nodes (LNs) indicate that the lung-based DCs can take up nanoparticles and migrate to the LNs. To embark in yet another imaging modality for tracking DC migration in a small mouse model we also develop a novel near-infrared (NIR) dye.
Advisors/Committee Members: J. Oliver McIntyre, Ph.D. (committee member), C. Chad Quarles, Ph.D. (committee member), Wellington Pham, Ph.D. (Committee Chair).
Subjects/Keywords: nebulization; nanoparticles; Immunotherapy; NIR dye
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bright, V. R. (2012). Multimodal nanoparticles for cancer therapy and imaging. (Thesis). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14622
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Bright, Vanessa Rochelle. “Multimodal nanoparticles for cancer therapy and imaging.” 2012. Thesis, Vanderbilt University. Accessed March 05, 2021.
http://hdl.handle.net/1803/14622.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Bright, Vanessa Rochelle. “Multimodal nanoparticles for cancer therapy and imaging.” 2012. Web. 05 Mar 2021.
Vancouver:
Bright VR. Multimodal nanoparticles for cancer therapy and imaging. [Internet] [Thesis]. Vanderbilt University; 2012. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/1803/14622.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Bright VR. Multimodal nanoparticles for cancer therapy and imaging. [Thesis]. Vanderbilt University; 2012. Available from: http://hdl.handle.net/1803/14622
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University College London (University of London)
20.
Baban, Babak.
The evaluation of a heat-killed suspension of Mycobacterium vaccae as an immunomodulating agent in the treatment of cancer.
Degree: PhD, 1998, University College London (University of London)
URL: https://discovery.ucl.ac.uk/id/eprint/10102229/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284829
► In the view of side effects and many other problems of conventional methods in treating cancer such as chemotherapy or radiotherapy, now a days, immunotherapy…
(more)
▼ In the view of side effects and many other problems of conventional methods in treating cancer such as chemotherapy or radiotherapy, now a days, immunotherapy has appeared as a very important and effective factor in combatting cancer. There have been many attempts to stimulate or regulate the various types of immune responses and to manipulate the immunological processes and diseases. These modulators for the immune system include products of bacteria and viruses and a multitude of chemicals, antigens, antibodies, other cellular and natural products, and cells. The advance in this area has had a revolutionary impact on the thinking and practice of cancer research and treatment. Immunotherapy can mobilises and utilises the body's natural factors and processes; ultimately, to restore the normal states. Since many biological and immunological agents are natural materials and specific for certain processes, they may, therefore, be better than conventional drugs in leaving the normal cells untouched and far more effective in eliminating the defects. Many biological and immunological agents have already been used in clinical trials and have been approved for clinical use. Already researchers are investigating new approaches to minimize the side effects and to maximise the benefits by using different type or mixture of biological agents in cancer patients. Due to the ability of Mycobacterium vaccae (M. vaccae) in stimulating and shifting the immune response toward the beneficial one (TH1 type of immune response) in cancer treatment, in this study, M. vaccae has been used as an immunotherapeutic agent in patients with advanced melanoma and prostate cancer who have failed all other conventional treatments. The effects of M.vaccae on these patients have been assessed both clinically and immunologically. For immunological evaluation, among some other methods which were tried, because of its efficiency, flow cytometry has been used as the main immunological evaluation tool in this sudy. During 18 months, all patients were monitored and followed up very carefully and many encouraging clinical and immunological results were found. Animal models were also used in this study.
Subjects/Keywords: 610; Immunotherapy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Baban, B. (1998). The evaluation of a heat-killed suspension of Mycobacterium vaccae as an immunomodulating agent in the treatment of cancer. (Doctoral Dissertation). University College London (University of London). Retrieved from https://discovery.ucl.ac.uk/id/eprint/10102229/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284829
Chicago Manual of Style (16th Edition):
Baban, Babak. “The evaluation of a heat-killed suspension of Mycobacterium vaccae as an immunomodulating agent in the treatment of cancer.” 1998. Doctoral Dissertation, University College London (University of London). Accessed March 05, 2021.
https://discovery.ucl.ac.uk/id/eprint/10102229/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284829.
MLA Handbook (7th Edition):
Baban, Babak. “The evaluation of a heat-killed suspension of Mycobacterium vaccae as an immunomodulating agent in the treatment of cancer.” 1998. Web. 05 Mar 2021.
Vancouver:
Baban B. The evaluation of a heat-killed suspension of Mycobacterium vaccae as an immunomodulating agent in the treatment of cancer. [Internet] [Doctoral dissertation]. University College London (University of London); 1998. [cited 2021 Mar 05].
Available from: https://discovery.ucl.ac.uk/id/eprint/10102229/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284829.
Council of Science Editors:
Baban B. The evaluation of a heat-killed suspension of Mycobacterium vaccae as an immunomodulating agent in the treatment of cancer. [Doctoral Dissertation]. University College London (University of London); 1998. Available from: https://discovery.ucl.ac.uk/id/eprint/10102229/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284829

McMaster University
21.
Afsahi, Arya.
Development of novel chimeric receptors for delivery of costimulation to tumor-reactive engineered T cells.
Degree: MSc, 2015, McMaster University
URL: http://hdl.handle.net/11375/18413
► Introduction: Manipulation of the immune system to eliminate cancer, known as cancer immunotherapy, is an emerging field that has shown impressive clinical success and promise.…
(more)
▼ Introduction: Manipulation of the immune system to eliminate cancer, known as cancer immunotherapy, is an emerging field that has shown impressive clinical success and promise. Adoptive transfer of T cells engineered for tumor reactivity is an avenue of therapy for patients with previously untreatable disease. Our lab has developed a novel chimeric receptor, called a T cell antigen coupler (TAC), which redirects T cell cytotoxicity towards a tumor target. Although considerably effective, this receptor does not provide T cell costimulation necessary for optimal anti-tumor effectiveness.
Methods: We explored two methods to deliver costimulation to TAC-engineered T cells. First, we designed a receptor to be utilized in conjunction with the TAC in a dual receptor system. This chimeric costimulatory receptor (CCR) was generated by fusion of the T cell TIGIT and CD28 receptors. In our second approach, we investigated direct incorporation of costimulatory domains into the TAC design. To do so, we substituted in regions from the CD28 or 4-1BB costimulatory receptors.
Results: Three TIGIT/CD28 chimeras were successfully generated. Of these, two were well surface-expressed on primary human T cells. Despite testing of these receptors in several biological assays, we were unable to confirm functionality of these receptors in transmitting CD28 signals. We next generated the 4-1BB and CD28TAC variants. The 4-1BBTAC was poorly surface-expressed
M.Sc Thesis – Arya Afsahi McMaster University – Medical Sciences
iv
and was difficult to introduce into T cells at high efficiency. The CD28TAC-variant was virtually absent from the T cell surface membrane. Further analysis indicated that the CD28TAC was retained in the endoplasmic reticulum (ER) and the 4-1BBTAC was produced at an extremely low amount.
Conclusions: Our investigation into delivery of costimulation through a novel CCR or TAC receptor was inconclusive. We recommend several optimizations to both receptor design and experimental analysis to further elucidate the potential of these receptors.
Thesis
Master of Science (MSc)
Advisors/Committee Members: Bramson, Jonathan, Medical Sciences (Molecular Virology and Immunology Program).
Subjects/Keywords: Immunology; T cell; Cancer; Immunotherapy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Afsahi, A. (2015). Development of novel chimeric receptors for delivery of costimulation to tumor-reactive engineered T cells. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/18413
Chicago Manual of Style (16th Edition):
Afsahi, Arya. “Development of novel chimeric receptors for delivery of costimulation to tumor-reactive engineered T cells.” 2015. Masters Thesis, McMaster University. Accessed March 05, 2021.
http://hdl.handle.net/11375/18413.
MLA Handbook (7th Edition):
Afsahi, Arya. “Development of novel chimeric receptors for delivery of costimulation to tumor-reactive engineered T cells.” 2015. Web. 05 Mar 2021.
Vancouver:
Afsahi A. Development of novel chimeric receptors for delivery of costimulation to tumor-reactive engineered T cells. [Internet] [Masters thesis]. McMaster University; 2015. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/11375/18413.
Council of Science Editors:
Afsahi A. Development of novel chimeric receptors for delivery of costimulation to tumor-reactive engineered T cells. [Masters Thesis]. McMaster University; 2015. Available from: http://hdl.handle.net/11375/18413

Boston University
22.
Kim, Susie.
Recent advancements in cancer immunotherapeutics.
Degree: MS, Medical Sciences, 2015, Boston University
URL: http://hdl.handle.net/2144/16217
► Cancer affects a wide range of organs and tissues within the body and epidemiologically is forecasted to affect almost half of the world's population. As…
(more)
▼ Cancer affects a wide range of organs and tissues within the body and epidemiologically is forecasted to affect almost half of the world's population. As an industry, cancer therapeutics represent a booming field. Standard treatment options, however, still heavily rely upon chemotherapeutics developed over fifty years ago. The past decade has seen a huge proliferation of different types of cancer drugs. Recently, an entirely new class of drugs has been unveiled and holds promising results of preventing further relapse incidents. Immunotherapeutics come in many varieties and currently several strategies are under intense investigation. Because these drugs harness the body's own immune system to specifically attack tumor cells, these drugs hold an advantage to current therapeutic options in that they induce notably less severe side effects, facilitating patients' abilities to maintain quality of life. In addition, these drugs potentially hold the promise to cure certain types of cancer, as the body's memory T cells will prevent relapse of the same tumor type. This review will focus on dendritic cell-based therapies, which attempt to program these antigen-presenting cell types to prime T cell responses, checkpoint blockade drugs that inhibit immunosuppression, and neoadjuvants that aim to render the surrounding tumor microenvironment more susceptible for immune attack. In addition, some documented and projected downsides to immunotherapeutics will be discussed, as well as the need to combine multiple modalities in order to create an effective and personalized treatment regimen for cancer patients.
Subjects/Keywords: Medicine; Cancer; Immunotherapy; Review
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kim, S. (2015). Recent advancements in cancer immunotherapeutics. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/16217
Chicago Manual of Style (16th Edition):
Kim, Susie. “Recent advancements in cancer immunotherapeutics.” 2015. Masters Thesis, Boston University. Accessed March 05, 2021.
http://hdl.handle.net/2144/16217.
MLA Handbook (7th Edition):
Kim, Susie. “Recent advancements in cancer immunotherapeutics.” 2015. Web. 05 Mar 2021.
Vancouver:
Kim S. Recent advancements in cancer immunotherapeutics. [Internet] [Masters thesis]. Boston University; 2015. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/2144/16217.
Council of Science Editors:
Kim S. Recent advancements in cancer immunotherapeutics. [Masters Thesis]. Boston University; 2015. Available from: http://hdl.handle.net/2144/16217

University of California – San Francisco
23.
Williams, Jasper Zee.
Engineering T cells with diverse mechanisms for improved tumor recognition precision.
Degree: Pharmaceutical Sciences and Pharmacogenomics, 2019, University of California – San Francisco
URL: http://www.escholarship.org/uc/item/0zn3g33t
► Engineered T cells are proven cancer therapeutics capable of executing potent antigen-dependent cell killing, and have gained FDA-approval after unprecedented results against certain blood cancers.…
(more)
▼ Engineered T cells are proven cancer therapeutics capable of executing potent antigen-dependent cell killing, and have gained FDA-approval after unprecedented results against certain blood cancers. However, successful treatment of solid tumors has been limited in large part by the lack of targetable antigens that are not also expressed in healthy tissues, as exhibited by ON-target OFF-tumor cross-reactive fatal toxicities seen in various human trials. An advantage of cell-based therapies is that cells can “compute” and execute more sophisticated programs than traditional drugs. Combinatorial antigen recognition has recently been introduced to overcome ON-target OFF-tumor toxicity limitations associated with traditional single antigen-targeted T cell therapies. This dissertation focuses on developing T cell engineering and biomaterials toolkits to expand the capabilities of combinatorial antigen-sensing T cell therapies. First presented is a set of approaches that use synNotch receptors and other synthetic receptors to program T cells with a diverse array of novel combinatorial antigen sensing circuits. It is shown that these Boolean logic-gated synNotch T cells can be engineered to sense both extracellular and intracellular antigens, target up to 3 antigens, integrate positive and negative regulation, and incorporate bispecific receptors. These abilities could enable engineering therapeutic T cells with the ability to target truly tumor-specific antigen combination signatures identified via bioinformatic analysis of antigen expression in cancer versus healthy cells. Also presented is a system to engineer T cells to recognize an orthogonal cue on biocompatible particles and incorporate this detection into combinatorial antigen-sensing circuits to specifically kill antigen positive tumor cells only in the presence of the particles. Using particles to control therapeutic cell activity in the body has the potential to enhance safety by enabling dynamic, local user-control of engineered cells during treatment. Together, the technologies presented here facilitate the development of engineered T cells to safely target a broader range of cancers. The toolkits developed here can be used to engineer T cell therapies to target cancer cells with significantly improved precision by taking advantage of our modern capabilities in cancer informatics, cell engineering, and biomaterials.
Subjects/Keywords: Pharmaceutical sciences; Antigens; Cancer; Immunotherapy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Williams, J. Z. (2019). Engineering T cells with diverse mechanisms for improved tumor recognition precision. (Thesis). University of California – San Francisco. Retrieved from http://www.escholarship.org/uc/item/0zn3g33t
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Williams, Jasper Zee. “Engineering T cells with diverse mechanisms for improved tumor recognition precision.” 2019. Thesis, University of California – San Francisco. Accessed March 05, 2021.
http://www.escholarship.org/uc/item/0zn3g33t.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Williams, Jasper Zee. “Engineering T cells with diverse mechanisms for improved tumor recognition precision.” 2019. Web. 05 Mar 2021.
Vancouver:
Williams JZ. Engineering T cells with diverse mechanisms for improved tumor recognition precision. [Internet] [Thesis]. University of California – San Francisco; 2019. [cited 2021 Mar 05].
Available from: http://www.escholarship.org/uc/item/0zn3g33t.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Williams JZ. Engineering T cells with diverse mechanisms for improved tumor recognition precision. [Thesis]. University of California – San Francisco; 2019. Available from: http://www.escholarship.org/uc/item/0zn3g33t
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto
24.
Berinstein, Elliot.
The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1.
Degree: 2016, University of Toronto
URL: http://hdl.handle.net/1807/90143
► The adoptive transfer of T lymphocytes expressing chimeric antigen receptors (CARs) has become a promising treatment for various cancers. CARs have been shown to redirect…
(more)
▼ The adoptive transfer of T lymphocytes expressing chimeric antigen receptors (CARs) has become a promising treatment for various cancers. CARs have been shown to redirect the cytotoxicity of T lymphocytes towards cancerous cells independent of the interactions between T cell receptors and major histocompatibility complexes. Given that CARs tie together an extracellular recognition domain with intracellular signaling domains of immune cells, there exists flexibility in designing CARs specific for different antigens in order to target different malignancies.
Here, we established murine antibodies specific for CD138 with the goal of designing a novel CAR. We designed a 2nd generation CAR using a single chain variable fragment derived from the 3E9B6 monoclonal antibody as the extracellular recognition domain. The expression of the 3E9B6 HL CAR specifically enhanced the cytotoxicity of the NK-92 cell line against CD138+ cells. Downstream activation of ZAP70 in NK-92 3E9B6 HL CAR cells was also dependent on the presence of CD138+ target cells. This work shows that the 3E9B6 HL CAR is functionally able to recognize CD138 and to initiate the CD3Îś activation pathway.
M.Sc.
2018-08-09 00:00:00
Advisors/Committee Members: Medin, Jeffrey A, Medical Biophysics.
Subjects/Keywords: Cancer; Gene Therapy; Immunotherapy; 0992
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Berinstein, E. (2016). The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/90143
Chicago Manual of Style (16th Edition):
Berinstein, Elliot. “The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1.” 2016. Masters Thesis, University of Toronto. Accessed March 05, 2021.
http://hdl.handle.net/1807/90143.
MLA Handbook (7th Edition):
Berinstein, Elliot. “The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1.” 2016. Web. 05 Mar 2021.
Vancouver:
Berinstein E. The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1. [Internet] [Masters thesis]. University of Toronto; 2016. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/1807/90143.
Council of Science Editors:
Berinstein E. The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1. [Masters Thesis]. University of Toronto; 2016. Available from: http://hdl.handle.net/1807/90143
25.
O'donnell, Kyle.
Avian IgY As An Immunotherapy For Flaviviral Infections.
Degree: PhD, Biomedical Sciences, 2019, University of North Dakota
URL: https://commons.und.edu/theses/2478
► Flaviviruses compose a group of positive single strand RNA viruses. This group possess 70 individual viruses that cause disease in humans and animals. This…
(more)
▼ Flaviviruses compose a group of positive single strand RNA viruses. This group possess 70 individual viruses that cause disease in humans and animals. This group contains the most prevalent arbovirus dengue virus (DENV) and a recently emerging arbovirus zika virus (ZIKV). Both DENV and ZIKV represent significant world health threats and both viruses, at the moment, are contained to tropical and sub tropical regions due to vector habitat restrictions. DENV can cause severe hemorrhagic fever termed dengue hemorrhagic fever and dengue shock syndrome depending on the extent of vascular permeability. The disease burden attributed to dengue infection is approximately 390 million infections per year. Of these infections, 96 million will result in clinical disease and 500,000 patients require hospitalization resulting in 25,000 deaths a year. ZIKV presents a less severe disease pathology, with a majority of infections in healthy adults being asymptomatic. The more severe infections in adults result in an autoimmune disease called Guillain-Barre syndrome. What caused the world health organization to declare ZIKV a world health emergency in 2016 is the viruses’ ability to transverse the placenta barrier and infect a developing fetus. The most severe symptom associated with in utero infection is the development of microcephaly, which leads to severe cognitive impairment. As case studies expand and the disease pathology of ZIKV is more fully understood a class of symptoms termed congenital zika syndrome fully classifies the extent of cognitive abnormalities induced by this virus. A commonality of these two viruses is that there are no approved treatments for either of these viral infections. A vaccine for DENV was recently introduced, but due to immunological complications it was withdrawn from distribution. A significant issue to combat with the development of therapies for dengue and zika viral infection is the induction of antibody dependent enhancement (ADE). ADE is mediated when cross-reactive low affinity antibodies bind to the virus and are internalized via the FcR on myeloid cells, but do not neutralize the virus resulting in an induction of pro-inflammatory cytokines and increased viral titer. In the studies presented here we hypothesized that the utilization of avian IgY, which does not interact with mammalian Fc receptors, would provide a viable therapy for ZIKV and DENV viral infection. Polyvalent anti-ZIKV IgY was purified from eggs of ZIKV immunized geese. The purified anti-ZIKV IgY preparation was assessed for it’s ability to neutralize ZIKV infection in vitro and in vivo. We also assessed for the ability of polyvalent anti-ZIKV IgY to enhance viral infection in vitro. Our data suggests that anti-ZIKV IgY is able to neutralize ZIKV infection in vitro and in vivo without inducing ADE. Our data also demonstrates novel viral epitopes recognized in our polyvalent anti-ZIKV IgY preparation. Previously our lab had established that polyvalent anti-DENV IgY was able to neutralize ZIKV infection in vitro and in vivo…
Advisors/Committee Members: David S. Bradley.
Subjects/Keywords: Dengue; Flavivirus; IgY; Immunotherapy; Zika
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APA (6th Edition):
O'donnell, K. (2019). Avian IgY As An Immunotherapy For Flaviviral Infections. (Doctoral Dissertation). University of North Dakota. Retrieved from https://commons.und.edu/theses/2478
Chicago Manual of Style (16th Edition):
O'donnell, Kyle. “Avian IgY As An Immunotherapy For Flaviviral Infections.” 2019. Doctoral Dissertation, University of North Dakota. Accessed March 05, 2021.
https://commons.und.edu/theses/2478.
MLA Handbook (7th Edition):
O'donnell, Kyle. “Avian IgY As An Immunotherapy For Flaviviral Infections.” 2019. Web. 05 Mar 2021.
Vancouver:
O'donnell K. Avian IgY As An Immunotherapy For Flaviviral Infections. [Internet] [Doctoral dissertation]. University of North Dakota; 2019. [cited 2021 Mar 05].
Available from: https://commons.und.edu/theses/2478.
Council of Science Editors:
O'donnell K. Avian IgY As An Immunotherapy For Flaviviral Infections. [Doctoral Dissertation]. University of North Dakota; 2019. Available from: https://commons.und.edu/theses/2478

Victoria University of Wellington
26.
Cameron, Alanna.
Targeted BRAF inhibitors: Immunological effects and combination with immunotherapy.
Degree: 2015, Victoria University of Wellington
URL: http://hdl.handle.net/10063/4937
► Metastatic melanoma is the most aggressive form of skin cancer, associated with a poor prognosis, and the incidence worldwide is increasing. Recently, selective mutant BRAF…
(more)
▼ Metastatic melanoma is the most aggressive form of skin cancer, associated with a poor prognosis, and the incidence worldwide is increasing. Recently, selective mutant BRAF inhibitors and checkpoint blockade
immunotherapy have advanced clinical treatment of metastatic melanoma. However, efficacy of these therapies individually is limited. Combining treatments may allow BRAF inhibition to augment
immunotherapy by increasing tumour antigen availability and improving immune system targeting of tumours. The success of this approach depends upon fully elucidating immunological interactions of BRAF inhibitors, and optimizing combination strategies.
To study the immunological effects of BRAF inhibitors and their combination with
immunotherapy, novel murine BrafV600E Pten-/- Cdkn2a cell lines were characterized. These were found to be moderately sensitive to BRAF inhibition compared with the widely used human BRAFV600E cell lines A375 and SK-mel-5. In vitro targeted BRAF inhibition was shown to induce cell death through apoptosis, and partially reverse melanoma-mediated immunosuppression by human melanoma cell lines.
Utilising subcutaneously injected syngeneic, murine BRAFV600E cell lines, the BRAF inhibitor PLX4720 was shown to decrease tumour growth in vivo. Host immune involvement in BRAF inhibitor efficacy was determined by comparing PLX4720 treatment in NOD/Scid and C57BL/6 mice. PLX4720 control of tumour growth was significantly less effective in immunocompromised mice, resulting in reduced survival advantage. These findings demonstrate that the anti-tumour effects of mutant BRAF inhibitors are partially immune dependent, although the nature of this immune involvement remains to be defined. It was further shown that BRAFV600E inhibition directly affected immune responses. In vitro, both human and murine T cell activation were boosted by low concentrations of mutant BRAF inhibitors. This was confirmed in vivo, with antigen-specific T cell proliferation significantly increased by PLX4720 treatment.
The final chapters of this thesis explored the combination of active
immunotherapy with targeted BRAF inhibition. A vaccine was devised that consisted of irradiated, autologous tumour cells loaded with the adjuvant α-galactosylceramide. This vaccine was shown to be effective in both prophylactic and therapeutic settings in a BRAFV600E melanoma model. Mechanistically, vaccine increased effector T cell responses and decreased frequencies of Tregs. Vaccine efficacy was CD4⁺ T cell-dependent, and did not require CD8⁺ T cells. Combination of vaccine with targeted BRAF inhibition was investigated in different settings. A combination therapy strategy was developed that achieved additive, but not synergistic benefit. Additionally, targeting specific aspects of the tumour microenvironment that may confer tumour resistance to BRAF inhibitor-mediated cell death was investigated. Both depletion of Tregs and inhibition of TNFα were explored, but did not result in a significant improvement in therapy.
In summary, the studies…
Advisors/Committee Members: Berridge, Michael, Herst, Patries.
Subjects/Keywords: Melanoma; Immunotherapy; BRAF inhibitors
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Cameron, A. (2015). Targeted BRAF inhibitors: Immunological effects and combination with immunotherapy. (Doctoral Dissertation). Victoria University of Wellington. Retrieved from http://hdl.handle.net/10063/4937
Chicago Manual of Style (16th Edition):
Cameron, Alanna. “Targeted BRAF inhibitors: Immunological effects and combination with immunotherapy.” 2015. Doctoral Dissertation, Victoria University of Wellington. Accessed March 05, 2021.
http://hdl.handle.net/10063/4937.
MLA Handbook (7th Edition):
Cameron, Alanna. “Targeted BRAF inhibitors: Immunological effects and combination with immunotherapy.” 2015. Web. 05 Mar 2021.
Vancouver:
Cameron A. Targeted BRAF inhibitors: Immunological effects and combination with immunotherapy. [Internet] [Doctoral dissertation]. Victoria University of Wellington; 2015. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/10063/4937.
Council of Science Editors:
Cameron A. Targeted BRAF inhibitors: Immunological effects and combination with immunotherapy. [Doctoral Dissertation]. Victoria University of Wellington; 2015. Available from: http://hdl.handle.net/10063/4937

University College London (University of London)
27.
Seah, Geok Teng.
Type-2 cytokines in the immunopathology of tuberculosis.
Degree: PhD, 2000, University College London (University of London)
URL: https://discovery.ucl.ac.uk/id/eprint/10101028/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325816
► Immune correlates of protective and deleterious host responses in human tuberculosis are not well understood, but this knowledge is central to the design of new…
(more)
▼ Immune correlates of protective and deleterious host responses in human tuberculosis are not well understood, but this knowledge is central to the design of new immunotherapeutic and vaccination strategies. Interest was focused on type-2 cytokines in the immunopathology of human tuberculosis in this work because exacerbation of disease coincides temporally with the emergence of type-2 responses in murine tuberculosis, but the human data had been inconclusive. A novel, sensitive method of measuring low copy number cytokines with a 5-log detection range was developed and validated for studying type-2 cytokine messenger ribonucleic acid (mRNA) production in unstimulated human cells, then applied to a clinical tuberculosis study. When compared to healthy tuberculin-positive tuberculosis contacts, tuberculosis patients expressed significantly higher levels of interleukin (IL)-4 and IL-13 mRNA which correlated with the radiographic extent of disease and serum immunoglobulin E levels, and did not always decline following treatment. Expression of the IL-4 splice-variant (IL4δ2) was also studied for the first time in this disease, and found to be bimodally distributed within the study population. Observations on human peripheral blood lymphocyte in vitro responses to M. tuberculosis sonicate (MtbS) antigens suggested that MtbS-activated lymphocytes were more susceptible to cytotoxic effects of TNF-α in the presence of IL-4. Lymphocytes expressing CD30 were particularly susceptible, and such cells had diminished levels of TNF-receptor-associated factor 2 (TRAF2) expression. TRAF2 mediates cytoprotective signalling pathways downstream of both TNF-α receptors and CD30. The levels of CD30 expression and IL-4 mRNA expression in MtbS-reactive lymphocytes were significantly higher than those in lymphocytes responding to M. vaccae sonicate antigens. CD30 expression was found to be IL-4-dependent in this model. A pathway linking apoptosis of MtbS-reactive lymphocytes to IL-4 production was proposed, and hence a potential mechanism by which type-2 cytokines may contribute to pathologic host responses in human tuberculosis.
Subjects/Keywords: 572; Immunotherapy
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Seah, G. T. (2000). Type-2 cytokines in the immunopathology of tuberculosis. (Doctoral Dissertation). University College London (University of London). Retrieved from https://discovery.ucl.ac.uk/id/eprint/10101028/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325816
Chicago Manual of Style (16th Edition):
Seah, Geok Teng. “Type-2 cytokines in the immunopathology of tuberculosis.” 2000. Doctoral Dissertation, University College London (University of London). Accessed March 05, 2021.
https://discovery.ucl.ac.uk/id/eprint/10101028/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325816.
MLA Handbook (7th Edition):
Seah, Geok Teng. “Type-2 cytokines in the immunopathology of tuberculosis.” 2000. Web. 05 Mar 2021.
Vancouver:
Seah GT. Type-2 cytokines in the immunopathology of tuberculosis. [Internet] [Doctoral dissertation]. University College London (University of London); 2000. [cited 2021 Mar 05].
Available from: https://discovery.ucl.ac.uk/id/eprint/10101028/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325816.
Council of Science Editors:
Seah GT. Type-2 cytokines in the immunopathology of tuberculosis. [Doctoral Dissertation]. University College London (University of London); 2000. Available from: https://discovery.ucl.ac.uk/id/eprint/10101028/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325816

University of Plymouth
28.
Goddard, Ruth Victoria.
Generation of in vitro B-cell chronic lymphocytic leukaemia-specific T cell responses using dendritic cells.
Degree: PhD, 2002, University of Plymouth
URL: http://hdl.handle.net/10026.1/2695
► Immunotherapy using dendritic cells has shown encouraging results in both haematological and non-haematological malignancies. In this study, monocyte-derived dendritic cells from patients with B-cell Chronic…
(more)
▼ Immunotherapy using dendritic cells has shown encouraging results in both haematological and non-haematological malignancies. In this study, monocyte-derived dendritic cells from patients with B-cell Chronic Lymphocytic Leukaemia were generated by culture in Interleukin-4 and Granulocyte Macrophage-Colony Stimulating Factor. Lysate-pulsed autologous dendritic cells were used as antigen presenting cells in co-culture with autologous B-cell Chronic Lymphocytic Leukaemia T-cells. B-cell Chronic Lymphocytic Leukaemia T-cells stimulated with B-cell Chronic Lymphocytic Leukaemia lysate-pulsed autologous dendritic cells showed a significant increase in cell surface expression of Interleukin-2 Receptor (CD25), Interferongamma secretion and cytotoxicity against autologous B-cell Chronic Lymphocytic Leukaemia B-cell targets hut not against targets from healthy volunteers. Responses were only stimulated by the B-cell Chronic Lymphocytic Leukaemia B cell lysate. Cytotoxicity was Major Histocompatibility Complex Class II restricted. The addition of maturation agents such as Lipopolysaccharide, Tumour Necrosis Factor-alpha and Polyriboinosinic Polyribocytidylic Acid to monocyte derived dendritic cells was unsuccessful at increasing anti-tumour responses. Pre-treatment of T cells with Interleukin-15 before stimulation by lysate pulsed autologous dendritic cells increased numbers of activated cells, cytokine secretion and specific cytotoxicity to B-cell Chronic Lymphocytic Leukaemia 8-cells. Fusion of monocyte derived dendritic cells and B-cell Chronic Lymphocytic Leukaemia B-cells generated both Major Histocompatibility Complex Class I and Class II restricted cytotoxicity to B-cell Chronic Lymphocytic Leukaemia B-cell targets. When B-cell lysates were analysed using reducing sodium dodecyl sulphate-polyacrylamide gel electrophoresis, a B-cell Chronic Lymphocytic Leukaemia specific hand at 42,000 Dalton and other patient specific bands were observed. Only the 65,000 Dalton and 42,000 Dalton hands were capable of stimulating comparable T cell responses as the whole lysate. The 65,000 Dalton band from normal healthy volunteers showed a dominant peptide that closely matched Human Serum Albumin. The 42,000 Dalton band from B-cell Chronic Lymphocytic Leukaemia patients showed a possible match with Human Actin.
Subjects/Keywords: 616; Immunotherapy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Goddard, R. V. (2002). Generation of in vitro B-cell chronic lymphocytic leukaemia-specific T cell responses using dendritic cells. (Doctoral Dissertation). University of Plymouth. Retrieved from http://hdl.handle.net/10026.1/2695
Chicago Manual of Style (16th Edition):
Goddard, Ruth Victoria. “Generation of in vitro B-cell chronic lymphocytic leukaemia-specific T cell responses using dendritic cells.” 2002. Doctoral Dissertation, University of Plymouth. Accessed March 05, 2021.
http://hdl.handle.net/10026.1/2695.
MLA Handbook (7th Edition):
Goddard, Ruth Victoria. “Generation of in vitro B-cell chronic lymphocytic leukaemia-specific T cell responses using dendritic cells.” 2002. Web. 05 Mar 2021.
Vancouver:
Goddard RV. Generation of in vitro B-cell chronic lymphocytic leukaemia-specific T cell responses using dendritic cells. [Internet] [Doctoral dissertation]. University of Plymouth; 2002. [cited 2021 Mar 05].
Available from: http://hdl.handle.net/10026.1/2695.
Council of Science Editors:
Goddard RV. Generation of in vitro B-cell chronic lymphocytic leukaemia-specific T cell responses using dendritic cells. [Doctoral Dissertation]. University of Plymouth; 2002. Available from: http://hdl.handle.net/10026.1/2695
29.
Thomas, Myles Duncan.
Production and characterisation of novel human monoclonal antibodies against malignant melanoma.
Degree: PhD, 1995, University of East London
URL: https://repository.uel.ac.uk/item/86q8w
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262193
► Malignant melanoma is an immunogenic tumour capable of inducing a humoral immune response, as shown by tumour-reactive serum antibody in patients. Lack of effective chemotherapy…
(more)
▼ Malignant melanoma is an immunogenic tumour capable of inducing a humoral immune response, as shown by tumour-reactive serum antibody in patients. Lack of effective chemotherapy in association with the immunogenic nature of the malignancy, has stimulated interest in the immunological management of the malignancy by antibody. Many mouse monoclonal antibodies against melanoma antigens have been developed, and some have been shown to induce tumour regression. However, a limitation on the use of mouse monoclonal antibodies in patients is the induction of an immune response against the immunising xenogeneic protein. The employment of human monoclonal antibodies, may be expected to reduce the patient's immune response against the allogeneic protein. Although more difficult to produce than mouse monoclonal antibodies, several human monoclonal antibodies have been established which induce tumour regression. Here I describe the establishment of mouse/human heterohybridomas producing human monoclonal antibody, from tumour-draining lymph nodes. A series of novel assay systems, initially developed and characterised using melanoma reactive mouse monoclonal antibodies, were sequentially employed for the selection of human antibody exhibiting high tumour specificity. Several clones producing melanoma reactive human antibody were established. Clone MDT. 1 was selected for further characterisation, because of its highly selective reactivity against viable melanoma and other neuroectodermal cell lines, but lack of reactivity against other common malignant and non-malignant cell lines. Such restricted cell reactivity is characteristic of reactivity with class 2 tumour associated antigens. MDT. 1 was shown, in ELISA, to exhibit reactivity to ganglioside antigens GD3, GD2, GD1b, GM3 and GM2. These antigens are commonly associatedw ith the malignant transformation of melanocytes and other neuroectodermal cells. Enzymatic modification of GM3, with neuraminidase, identified the reactive minimal essential epitope as Neua2- 3Galß1-4GIc-. Reactivity with rat monoclonal antibody 9G4 and molecular analysis showed MDT. 1 is encoded by the highly conserved VH4 gene, VH4-21. Like other VH4-21 encoded autoantibodies MDT. 1 exhibits reactivity with the cold agglutinin T. Analysis of the structures of `i' and sialogangliosides has identified similar structural epitopes, which may confer MDT. 1 reactivity. VH4-21 encoded autoantibody 216 exhibits similar reactivity with tumour associated ganglioside antigens as MDT. 1. Sialo-ganglioside/`i' reactive VH4-21 encoded antibodies, could therefore represent an important aspect of autoantibodies in the overall host immune response to tumour.
Subjects/Keywords: 610.28; Immunotherapy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Thomas, M. D. (1995). Production and characterisation of novel human monoclonal antibodies against malignant melanoma. (Doctoral Dissertation). University of East London. Retrieved from https://repository.uel.ac.uk/item/86q8w ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262193
Chicago Manual of Style (16th Edition):
Thomas, Myles Duncan. “Production and characterisation of novel human monoclonal antibodies against malignant melanoma.” 1995. Doctoral Dissertation, University of East London. Accessed March 05, 2021.
https://repository.uel.ac.uk/item/86q8w ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262193.
MLA Handbook (7th Edition):
Thomas, Myles Duncan. “Production and characterisation of novel human monoclonal antibodies against malignant melanoma.” 1995. Web. 05 Mar 2021.
Vancouver:
Thomas MD. Production and characterisation of novel human monoclonal antibodies against malignant melanoma. [Internet] [Doctoral dissertation]. University of East London; 1995. [cited 2021 Mar 05].
Available from: https://repository.uel.ac.uk/item/86q8w ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262193.
Council of Science Editors:
Thomas MD. Production and characterisation of novel human monoclonal antibodies against malignant melanoma. [Doctoral Dissertation]. University of East London; 1995. Available from: https://repository.uel.ac.uk/item/86q8w ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262193
30.
Šilanskas, Mantas.
Oncolytic viruses armed with immunostimulatory genes for cancer treatment.
Degree: Biology Education Centre, 2018, Uppsala UniversityUppsala University
URL: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-353153
► Cancer is a major health burden in modern society, costing millions of lives worldwide and negatively impacting many more. With increasing rates of cancer,…
(more)
▼ Cancer is a major health burden in modern society, costing millions of lives worldwide and negatively impacting many more. With increasing rates of cancer, there is a need for new approaches to its treatment. This is where immunotherapies step in, this a relatively new approach to cancer treatment which caught public’s attention only in recent years. The main goal of these therapies is to enhance and help immune cells to identify and kill tumor cells, thereby initiating the cycle of cancer immunity. In this project LOAd platform viruses were evaluated and compared for their ability to induce oncolysis in cancer cells and ability to produce immunostimulatory molecules. Established LOAd703 virus armed with CD40L and 4-1BBL transgenes was compared to new constructs LOAd732, LOAd780 and LOAd786. All three new viruses are armed with CD40L and 4-1BBL, but also have additional transgenes X, Y and Z, respectively. Specific molecules coded by these transgenes cannot be disclosed at this moment. All viruses demonstrated high competence in oncolysis of A549-lung, T24-bladder and 526-mel melanoma cancer cell lines and were able to express transgenes coding for CD40L and 4-1BBL in all cell lines. New viruses were able to induce expression of new transgenes in infected cells, except for LOAd780 infected cell which had low concentration of protein Y in their supernatants. Also dendritic cells matured using LOAd viruses were able to induce expansion of CMV-specific T cells and a major expansion of natural killer cells.
Subjects/Keywords: Cancer; Virus; Immunotherapy; Immunology; Immunologi
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Šilanskas, M. (2018). Oncolytic viruses armed with immunostimulatory genes for cancer treatment. (Thesis). Uppsala UniversityUppsala University. Retrieved from http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-353153
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Šilanskas, Mantas. “Oncolytic viruses armed with immunostimulatory genes for cancer treatment.” 2018. Thesis, Uppsala UniversityUppsala University. Accessed March 05, 2021.
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-353153.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Šilanskas, Mantas. “Oncolytic viruses armed with immunostimulatory genes for cancer treatment.” 2018. Web. 05 Mar 2021.
Vancouver:
Šilanskas M. Oncolytic viruses armed with immunostimulatory genes for cancer treatment. [Internet] [Thesis]. Uppsala UniversityUppsala University; 2018. [cited 2021 Mar 05].
Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-353153.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Šilanskas M. Oncolytic viruses armed with immunostimulatory genes for cancer treatment. [Thesis]. Uppsala UniversityUppsala University; 2018. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-353153
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
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