subject:(oncolytic virotherapy)

University of Newcastle

1. Chan, Eric. Low pathogenic human enteroviruses as novel anti-cancer agents against malignant glioma.

Degree: PhD, 2014, University of Newcastle

URL: http://hdl.handle.net/1959.13/1050162

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Research Doctorate - Doctor of Philosophy (PhD)

Malignant gliomas (MGs) are the most common tumours of the central nervous system (CNS) and respond poorly to… (more)

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Research Doctorate - Doctor of Philosophy (PhD)

Malignant gliomas (MGs) are the most common tumours of the central nervous system (CNS) and respond poorly to surgery, radiotherapy and chemotherapy. Despite conven- tional therapy, this disease is fatal within 1 to 2 years of the onset of symptoms. Preclinical studies have shown that low pathogenic human enteroviruses such as Coxsackievirus A21 (CVA21), CVA21-DAFv and Echovirus 1 (EV1) possess anti-cancer (oncolytic) potential against many different tumours, including melanoma, multiple myeloma, breast, prostate, gastric and ovarian cancer. The selective targeting of CVA21, CVA21-DAFv and EV1 is based on the overexpression of the cellular receptors intercellular adhesion molecule- 1 (ICAM-1), decay accelerating factor (DAF) and integrin α2β1 on the surface of many cancer cells compared to normal cells. The employment of CVA21 to control cancer progression is currently under Phase I/II clinical trials for the treatment of melanoma, breast, bladder, prostate and lung cancer. The bioselected variant of CVA21 (CVA21-DAFv) is an enhanced DAF-using phenotype, compared to the parental CVA21 strain which utilizes ICAM-1 and/or DAF. Moreover, EV1 infection requires the cell surface expression of integrin α2β1, enabling binding of the viral capsid, internalization, and subsequent lytic infection. Prior to the study of the potential use of these enteroviruses for the treatment of MG, screening for these such cellular receptors was performed by confirming mRNA gene expression profiles of ICAM-1, DAF and integrin α2β1 in cancerous brain tissues, in comparison to normal brain tissue biopsy material. The presence of these cellular receptors on the surface of glioma cells was also assessed using flow cytometry and immunohistochemical (IHC) staining. The in vitro screening to evaluate the oncolytic capacity of enteroviruses was subsequently performed in a range of established glioma cell lines (U87 MG, A172, T98G, U118 and GBM6) and normal brain cells (HCN-2). To further investigate the role of CVA21 or CVA21-DAFv in the treatment of MG, an orthotopic model of MG was established in athymic nude mice. To evaluate the efficacy of CVA21 or CVA21-DAFv as a single agent, mice bearing intracranial (i.c.) U87 MG-luc tumours were administered with either viruses. Mice were initially injected with a single administration into the tumour and subsequent intravenous (i.v.) doses of either viruses. In vivo, both CVA21 and CVA21-DAFv significantly reduced tumour growth early on in the study, but tumours eventually recurred. Given that oncolytic viruses may be used in the clinic together with existing treatment modalities such as chemotherapy, the combinatorial effects of human enteroviruses with a panel of standard of care chemotherapeutic agents [including temozolomide (TMZ), cyclophosphamide (CPA) and carboplatin (Cb)] were examined. The effects of these chemotherapeutic agents on human enterovirus oncolysis and viral replication were assessed in vitro to identify synergistic, additive or…

Advisors/Committee Members: University of Newcastle. Faculty of Health & Medicine, School of Biomedical Sciences and Pharmacy.

Subjects/Keywords: oncolytic virotherapy; malignant glioma; chemotherapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chan, E. (2014). Low pathogenic human enteroviruses as novel anti-cancer agents against malignant glioma. (Doctoral Dissertation). University of Newcastle. Retrieved from http://hdl.handle.net/1959.13/1050162

Chicago Manual of Style (16^th Edition):

Chan, Eric. “Low pathogenic human enteroviruses as novel anti-cancer agents against malignant glioma.” 2014. Doctoral Dissertation, University of Newcastle. Accessed April 14, 2021. http://hdl.handle.net/1959.13/1050162.

MLA Handbook (7^th Edition):

Chan, Eric. “Low pathogenic human enteroviruses as novel anti-cancer agents against malignant glioma.” 2014. Web. 14 Apr 2021.

Vancouver:

Chan E. Low pathogenic human enteroviruses as novel anti-cancer agents against malignant glioma. [Internet] [Doctoral dissertation]. University of Newcastle; 2014. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/1959.13/1050162.

Council of Science Editors:

Chan E. Low pathogenic human enteroviruses as novel anti-cancer agents against malignant glioma. [Doctoral Dissertation]. University of Newcastle; 2014. Available from: http://hdl.handle.net/1959.13/1050162

University of Guelph

2. AuYeung, Wing Ka Amanda. Immunological effects of oncolytic virotherapy in the context of a preclinical model of melanoma.

Degree: MS, Department of Pathobiology, 2017, University of Guelph

URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/11517

► Conventional therapies have demonstrated little to no extension in overall survival in the context of metastatic melanomas. As a result there is growing interest in… (more)

Subjects/Keywords: oncolytic virotherapy; cancer immunotherapy; melanoma

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APA (6^th Edition):

AuYeung, W. K. A. (2017). Immunological effects of oncolytic virotherapy in the context of a preclinical model of melanoma. (Masters Thesis). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/11517

Chicago Manual of Style (16^th Edition):

AuYeung, Wing Ka Amanda. “Immunological effects of oncolytic virotherapy in the context of a preclinical model of melanoma.” 2017. Masters Thesis, University of Guelph. Accessed April 14, 2021. https://atrium.lib.uoguelph.ca/xmlui/handle/10214/11517.

MLA Handbook (7^th Edition):

AuYeung, Wing Ka Amanda. “Immunological effects of oncolytic virotherapy in the context of a preclinical model of melanoma.” 2017. Web. 14 Apr 2021.

Vancouver:

AuYeung WKA. Immunological effects of oncolytic virotherapy in the context of a preclinical model of melanoma. [Internet] [Masters thesis]. University of Guelph; 2017. [cited 2021 Apr 14]. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/11517.

Council of Science Editors:

AuYeung WKA. Immunological effects of oncolytic virotherapy in the context of a preclinical model of melanoma. [Masters Thesis]. University of Guelph; 2017. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/11517

University of Newcastle

3. Smith, Lincoln. Investigation of coxsackievirus A21 as a potential treatment for pancreatic cancer.

Degree: PhD, 2018, University of Newcastle

URL: http://hdl.handle.net/1959.13/1391435

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Research Doctorate - Doctor of Philosophy (PhD)

Coxsackievirus A21 (CVA21) is a human specific, non-enveloped, 28 nm icosahedral, group C enterovirus with a single strand… (more)

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Research Doctorate - Doctor of Philosophy (PhD)

Coxsackievirus A21 (CVA21) is a human specific, non-enveloped, 28 nm icosahedral, group C enterovirus with a single strand positive sense RNA genome. CVA21 causes common cold symptoms upon infection in humans. CVA21 utilises intercellular adhesion molecule 1 (ICAM-1) and decay accelerating factor (DAF) for cell surface binding and cell entry of target cells. Cancer cells commonly overexpress ICAM-1 making them susceptible to CVA21 infection. Upon invasion of a host cell, viral progeny is produced through hijacking cellular machinery. Host cell lysis occurs, and virus is able to infect nearby and distant cells through systemic spread. Furthermore, cancer cell oncolysis may lead to recognition of specific tumour cell epitopes by the host’s immune system and generation of an anti-tumour immune response. CVA21 is a potentially efficacious anti-cancer agent for multiple cancer types in preclinical studies and is undergoing investigation in clinical trials as treatments for a range of cancer types with promising early stage results. Investigation of CVA21 as a potential treatment for pancreatic cancer in clinical trials will hopefully be initiated in the near future. Pancreatic cancer (PC) is the most lethal of all cancer types. PC has the worst survival rates of any cancer type and incidence continues to increase annually. Even though the genomic aberration profiles and molecular pathogenesis of PC are well documented there are still no early detection mechanisms for PC. Pancreatic cancer is characterised by PC cells supported by a dense desmoplastic reaction, composed primarily of pancreatic stellate cells (PSCs), that is highly tumour promoting, with rapid progression. Currently, there are no treatments that can adequately control the disease. Furthermore, present treatment options provide unsatisfactory toxicity and quality of life to suffering patients. Efficacious treatment options are rapidly needed. The oncolytic virus, CVA21, has great potential as a treatment for PC. The capacity to directly lyse tumour cells as well as prompt an adaptive anti-tumour immune response while proving to exert minimal levels of host adverse events makes CVA21 an ideal anti-cancer agent. Investigation of CVA21 as a potential treatment for PC in the preclinical setting was the major aim of this study. The key hypothesis for this project was that CVA21 would be an effective anti-cancer agent against pancreatic cancer due to high expression of viral entry receptors, ICAM-1 and/or DAF on PC and PSCs. Furthermore, CVA21 would have enhanced anti-tumour activity in combination with chemotherapeutic or immunotherapeutic agents. Such questions were addressed through specific in vitro tissue culture and immunohistochemical analyses, and in vivo mouse models. Initially the study determined the expression levels of CVA21 cell entry receptors, ICAM-1 and DAF, on the surface of PC and PSCs and compared these levels to normal pancreatic cells. Evaluation of expression levels were…

Advisors/Committee Members: University of Newcastle. Faculty of Health & Medicine, School of Biomedical Sciences and Pharmacy.

Subjects/Keywords: coxsackievirus A21; CVA21; pancreatic cancer; oncolytic virotherapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Smith, L. (2018). Investigation of coxsackievirus A21 as a potential treatment for pancreatic cancer. (Doctoral Dissertation). University of Newcastle. Retrieved from http://hdl.handle.net/1959.13/1391435

Chicago Manual of Style (16^th Edition):

Smith, Lincoln. “Investigation of coxsackievirus A21 as a potential treatment for pancreatic cancer.” 2018. Doctoral Dissertation, University of Newcastle. Accessed April 14, 2021. http://hdl.handle.net/1959.13/1391435.

MLA Handbook (7^th Edition):

Smith, Lincoln. “Investigation of coxsackievirus A21 as a potential treatment for pancreatic cancer.” 2018. Web. 14 Apr 2021.

Vancouver:

Smith L. Investigation of coxsackievirus A21 as a potential treatment for pancreatic cancer. [Internet] [Doctoral dissertation]. University of Newcastle; 2018. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/1959.13/1391435.

Council of Science Editors:

Smith L. Investigation of coxsackievirus A21 as a potential treatment for pancreatic cancer. [Doctoral Dissertation]. University of Newcastle; 2018. Available from: http://hdl.handle.net/1959.13/1391435

University of Minnesota

4. Berg, David. A Flexible Simulator for Oncolytic Viral Therapy.

Degree: MS, Biomedical Informatics and Computational Biology, 2015, University of Minnesota

URL: http://hdl.handle.net/11299/174710

► Developments in recombinant DNA technology have given researchers the ability to modify viruses so that they are highly selective towards cancer cells. Engineered viruses have… (more)

Subjects/Keywords: cancer; measles; monte carlo; oncolytic; simulation; virotherapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Berg, D. (2015). A Flexible Simulator for Oncolytic Viral Therapy. (Masters Thesis). University of Minnesota. Retrieved from http://hdl.handle.net/11299/174710

Chicago Manual of Style (16^th Edition):

Berg, David. “A Flexible Simulator for Oncolytic Viral Therapy.” 2015. Masters Thesis, University of Minnesota. Accessed April 14, 2021. http://hdl.handle.net/11299/174710.

MLA Handbook (7^th Edition):

Berg, David. “A Flexible Simulator for Oncolytic Viral Therapy.” 2015. Web. 14 Apr 2021.

Vancouver:

Berg D. A Flexible Simulator for Oncolytic Viral Therapy. [Internet] [Masters thesis]. University of Minnesota; 2015. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/11299/174710.

Council of Science Editors:

Berg D. A Flexible Simulator for Oncolytic Viral Therapy. [Masters Thesis]. University of Minnesota; 2015. Available from: http://hdl.handle.net/11299/174710

Louisiana State University

5. Fowlkes, Natalie Wall. Evaluation of Oncolytic and Immunomodulatory Potential of the HSV-1 Live-Attenuated Vaccine Strain VC2 in an Immunocompetent Murine Melanoma Model.

Degree: PhD, Comparative and Laboratory Animal Medicine, 2018, Louisiana State University

URL: https://digitalcommons.lsu.edu/gradschool_dissertations/4669

► Melanoma accounts for 90% of skin cancer-related deaths in humans. Treatment options for metastatic melanoma in people is very limited. Melanoma is considered to… (more)

▼ Melanoma accounts for 90% of skin cancer-related deaths in humans. Treatment options for metastatic melanoma in people is very limited. Melanoma is considered to be an immunogenic tumor, spurring interest in development of immunotherapies for the treatment of metastatic melanoma. Oncolytic virotherapy has been widely investigated. The first ever oncolytic virotherapy to receive FDA-approval is an HSV-1-based virus (Talimogene Laherperavec (T-Vec) or Imlygic) containing a transgene for human GM-CSF to enhance anti-tumor immune responses after injection. Durable response rate in human patients was only 16% despite impressive efficacy in anti-tumor effects in vitro and in murine tumor models. Novel viruses with enhanced immune-stimulating properties and improved efficacy and safety profiles are needed. Further, the lack of concordance of preclinical murine studies with results in human clinical trials highlights the need for improved murine tumor modeling strategies. Our laboratory developed the live-attenuated HSV-1 (VC2) vaccine strain, which has shown efficacy in protection against lethal intravaginal HSV-1 and HSV-2 challenge after a single intramuscular injection in mice. VC2 replicate efficiently in permissible cells but does not enter ganglionic axons. Further, VC2 is highly immunogenic generating strong cell-mediated and humoral immune responses. We developed an immunocompetent double-labeled murine melanoma model for testing the immune-modulating and adjuvant effects of oncolytic herpesviruses. Intratumoral virotherapy using VC2 resulted in significant increases in CD3+ T cells and IBA-1+ macrophages in the tumor microenvironment, but reduced expression of arginase-1, a marker of the M2, pro-tumorigenic macrophage phenotype. Median survival times (MST) of VC2 treated mice were nearly twice that of mock-treated controls. We also found that bioluminescence allows for more sensitive assessment of anti-tumor responses during the acute inflammatory phase of treatment during which pseudoprogression can result in misleading increases in tumor volumes using traditional caliper measurements. Our findings suggest that the remarkable immunogenicity of VC2 makes it a good candidate as a vector for tumor vaccine development and our model allows for sensitive assessment of response to therapy in the face of marked acute inflammation. These findings represent significant progress in viral vector development for cancer therapy and in modeling strategies for testing immune-stimulating anti-cancer therapies.

Subjects/Keywords: melanoma; cancer model; oncolytic virotherapy; HSV-1

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APA (6^th Edition):

Fowlkes, N. W. (2018). Evaluation of Oncolytic and Immunomodulatory Potential of the HSV-1 Live-Attenuated Vaccine Strain VC2 in an Immunocompetent Murine Melanoma Model. (Doctoral Dissertation). Louisiana State University. Retrieved from https://digitalcommons.lsu.edu/gradschool_dissertations/4669

Chicago Manual of Style (16^th Edition):

Fowlkes, Natalie Wall. “Evaluation of Oncolytic and Immunomodulatory Potential of the HSV-1 Live-Attenuated Vaccine Strain VC2 in an Immunocompetent Murine Melanoma Model.” 2018. Doctoral Dissertation, Louisiana State University. Accessed April 14, 2021. https://digitalcommons.lsu.edu/gradschool_dissertations/4669.

MLA Handbook (7^th Edition):

Fowlkes, Natalie Wall. “Evaluation of Oncolytic and Immunomodulatory Potential of the HSV-1 Live-Attenuated Vaccine Strain VC2 in an Immunocompetent Murine Melanoma Model.” 2018. Web. 14 Apr 2021.

Vancouver:

Fowlkes NW. Evaluation of Oncolytic and Immunomodulatory Potential of the HSV-1 Live-Attenuated Vaccine Strain VC2 in an Immunocompetent Murine Melanoma Model. [Internet] [Doctoral dissertation]. Louisiana State University; 2018. [cited 2021 Apr 14]. Available from: https://digitalcommons.lsu.edu/gradschool_dissertations/4669.

Council of Science Editors:

Fowlkes NW. Evaluation of Oncolytic and Immunomodulatory Potential of the HSV-1 Live-Attenuated Vaccine Strain VC2 in an Immunocompetent Murine Melanoma Model. [Doctoral Dissertation]. Louisiana State University; 2018. Available from: https://digitalcommons.lsu.edu/gradschool_dissertations/4669

University of Newcastle

6. Quah, Min Yuan. Enhancement of oncolytic coxasckievirus A21 with conventional chemotherapies and immune checkpoint inhibitors for the treatment of melanoma.

Degree: PhD, 2016, University of Newcastle

URL: http://hdl.handle.net/1959.13/1312749

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Research Doctorate - Doctor of Philosophy (PhD)

Malignant melanoma is one of the most aggressive and lethal cancers of the skin. Clinical reports have shown… (more)

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Research Doctorate - Doctor of Philosophy (PhD)

Malignant melanoma is one of the most aggressive and lethal cancers of the skin. Clinical reports have shown patients diagnosed with stage IV of the disease have no longer than five years to live. Depending on the sub-stage of the disease, median survival of patients is between 6 - 18 months. To date, current Food and Drug Administration (FDA) approved anticancer drugs for melanoma have demonstrated limited response rates, few complete remissions and no significant survival benefits. The development of new therapies to effectively eradicate malignant melanoma are desperately in need. Recent growth in the field of oncolytic virotherapy has led to an increased number of clinical trials and acceptance of tumour selective viruses as a promising anticancer strategy. Numerous viruses have emerged as potent oncolytic agents because of their capacity to preferentially infect and destroy cancer cells while leaving normal cells intact. Like most anticancer modalities, it is very likely that oncolytic virotherapy will be used in combination with other existing therapeutics. Numerous groups have begun to explore the possibility of combining oncolytic virotherapy with conventional cancer therapies. The combination of oncolytic virotherapy with other existing cancer therapies may be an effective strategy to overcome the barriers faced by either therapeutic agents when used as monotherapies. The Kuykendall strain of Coxsackievirus A21 (CVA21) is a naturally occurring common-cold virus that has the inherent capacity to preferentially infect and destroy malignant cells. The oncolytic properties of CVA21 as an anticancer agent have been demonstrated both in vitro and in vivo studies, against numerous types of cancer, including breast cancer, prostate cancer, glioma, multiple myeloma, non-small cell lung carcinoma, and melanoma. In the clinic, tumour regression was observed in both injectable and distant non-injected lesion without any significant adverse events. Despite CVA21’s impressive progress to date, it is becoming clear the oncolytic viruses (OVs) cannot be viewed as monotherapies. The current trend is for the combination of virotherapy with mainstream therapies. A fundamental requirement for the success of this strategy is that the combination does not interfere with the life cycle of the oncolytic virus from the point of viral entry, to the release of viral progeny. In Chapter 4, we demonstrated that not only does the co-administration of clinically relevant cytotoxic anticancer drugs such as dacarbazine, paclitaxel and carboplatin not interfere with replication cycle of CVA21, enhanced cell destruction of melanoma cells was achieved when both oncolytic agent and chemotherapy were combined. To determine whether actual synergism was present, we subjected our data to the Chou-Talalay median effect equation which provides a robust measurement of drug combination relationships based on combination index values. When the constant drug-ratio design was applied to our…

Advisors/Committee Members: University of Newcastle. Faculty of Health & Medicine, School of Biomedical Sciences and Pharmacy.

Subjects/Keywords: chemotherapy; melanoma; oncolytic coxsackievirus A21; skin cancers; oncolytic virotherapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Quah, M. Y. (2016). Enhancement of oncolytic coxasckievirus A21 with conventional chemotherapies and immune checkpoint inhibitors for the treatment of melanoma. (Doctoral Dissertation). University of Newcastle. Retrieved from http://hdl.handle.net/1959.13/1312749

Chicago Manual of Style (16^th Edition):

Quah, Min Yuan. “Enhancement of oncolytic coxasckievirus A21 with conventional chemotherapies and immune checkpoint inhibitors for the treatment of melanoma.” 2016. Doctoral Dissertation, University of Newcastle. Accessed April 14, 2021. http://hdl.handle.net/1959.13/1312749.

MLA Handbook (7^th Edition):

Quah, Min Yuan. “Enhancement of oncolytic coxasckievirus A21 with conventional chemotherapies and immune checkpoint inhibitors for the treatment of melanoma.” 2016. Web. 14 Apr 2021.

Vancouver:

Quah MY. Enhancement of oncolytic coxasckievirus A21 with conventional chemotherapies and immune checkpoint inhibitors for the treatment of melanoma. [Internet] [Doctoral dissertation]. University of Newcastle; 2016. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/1959.13/1312749.

Council of Science Editors:

Quah MY. Enhancement of oncolytic coxasckievirus A21 with conventional chemotherapies and immune checkpoint inhibitors for the treatment of melanoma. [Doctoral Dissertation]. University of Newcastle; 2016. Available from: http://hdl.handle.net/1959.13/1312749

University of Newcastle

7. Wong, Yvonne Vern Yee. Investigation of oncolytic coxsackievirus A21 as a potential treatment for lung cancer.

Degree: PhD, 2016, University of Newcastle

URL: http://hdl.handle.net/1959.13/1314627

►

Research Doctorate - Doctor of Philosophy (PhD)

Lung cancer is the most frequently diagnosed and the second most common mortalityrelated cancer in the world, with… (more)

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Research Doctorate - Doctor of Philosophy (PhD)

Lung cancer is the most frequently diagnosed and the second most common mortalityrelated cancer in the world, with the majority of cases diagnosed only at an advanced/late stage. Lung cancer is a complex malignant disease with numerous histological subtypes classified into two main categories, namely non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Conventional therapies, including surgery, radiation therapy and chemotherapy have yielded limited success in the treatment of lung cancer, especially in cases involving metastatic spread. Lung cancer is a difficult cancer to treat as it is a highly metastatic disease and consists of two main differing phenotypes which require differing treatment regimens. Therefore, there is the crucial need to develop new therapeutic strategies against this cancer type. Oncolytic virotherapy, a rapidly growing field in which a broad range of viruses have been developed to specifically attack and target cancer cells, is one of the few novel approaches for the treatment of lung cancer. Among the various viruses used in oncolytic virotherapy, of particular focus is Coxsackievirus A21 (CVA21), a wild-type naturally occurring positive-sense single stranded RNA human enterovirus that demonstrated potent oncolytic effects against a range of cancer types such as melanoma, breast, prostate, glioma, multiple myeloma, pancreatic, and bladder carcinoma. CVA21 selectively targets and lytically infects susceptible cancer cells that overexpress the viral cellular receptors, intercellular adhesion molecule-1 (ICAM-1) and/or decay accelerating factor (DAF). In this dissertation, CVA21 is shown to be an effective oncolytic agent against lung cancer, particularly of the NSCLC phenotype. A proprietary formulation of CVA21 (commercial trade name CAVATA^TM) is currently being evaluated in several Phase I and II clinical trials across a variety of cancer indications. Previous trials of CVA21 for the treatment of malignant melanoma have shown that it is generally well-tolerated in patients. The oncolytic efficacy of CVA21 against lung cancer was further investigated as either a single agent therapy or in combination with chemotherapy, in particular the current standard of care agent, docetaxel. Until the introduction of docetaxel (Taxotere®, Sanofi-aventis, Paris, France), a semisynthetic taxane drug, no previous chemotherapeutic agents displayed significant improvement in survival or quality of life in randomised trials of second-line treatment of advanced or metastatic NSCLC. Docetaxel was the first chemotherapeutic agent to show efficacy by increasing the survival and quality of life in lung cancer patients when given as a single agent first- and second-line treatment, and as a first-line in platinumbased doublet therapy. Docetaxel works by primarily stimulating microtubule assembly and polymerisation, leading ultimately to cell cycle arrest and death. Through the hyperstabilisation of growing microtubules, the drug upsets the…

Advisors/Committee Members: University of Newcastle. Faculty of Health & Medicine, School of Biomedical Sciences and Pharmacy.

Subjects/Keywords: oncolytic coxsackievirus A21; lung cancer; mortalityrelated cancer; oncolytic virotherapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wong, Y. V. Y. (2016). Investigation of oncolytic coxsackievirus A21 as a potential treatment for lung cancer. (Doctoral Dissertation). University of Newcastle. Retrieved from http://hdl.handle.net/1959.13/1314627

Chicago Manual of Style (16^th Edition):

Wong, Yvonne Vern Yee. “Investigation of oncolytic coxsackievirus A21 as a potential treatment for lung cancer.” 2016. Doctoral Dissertation, University of Newcastle. Accessed April 14, 2021. http://hdl.handle.net/1959.13/1314627.

MLA Handbook (7^th Edition):

Wong, Yvonne Vern Yee. “Investigation of oncolytic coxsackievirus A21 as a potential treatment for lung cancer.” 2016. Web. 14 Apr 2021.

Vancouver:

Wong YVY. Investigation of oncolytic coxsackievirus A21 as a potential treatment for lung cancer. [Internet] [Doctoral dissertation]. University of Newcastle; 2016. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/1959.13/1314627.

Council of Science Editors:

Wong YVY. Investigation of oncolytic coxsackievirus A21 as a potential treatment for lung cancer. [Doctoral Dissertation]. University of Newcastle; 2016. Available from: http://hdl.handle.net/1959.13/1314627

University of Miami

8. Heiber, Joshua F. Characterization and Development of Vesicular Stomatitis Virus For Use as an Oncolytic Vector.

Degree: PhD, Microbiology and Immunology (Medicine), 2011, University of Miami

URL: https://scholarlyrepository.miami.edu/oa_dissertations/600

► Oncolytic virotherapy is emerging as a new treatment option for cancer patients. At present, there are relatively few oncolytic virus clinical trials that are underway… (more)

▼ Oncolytic virotherapy is emerging as a new treatment option for cancer patients. At present, there are relatively few oncolytic virus clinical trials that are underway or have been conducted, however one virus that shows promise in pre-clinical models is Vesicular Stomatitis Virus (VSV). VSV is a naturally occurring oncolytic rhabdovirus that has the ability to preferentially replicate in and kill malignant versus normal cells. VSV also has a low seroprevalence, minimal associated morbidity and mortality in humans, and simple non-integrating genome that can be genetically manipulated, making it an optimal oncolytic vector. Currently, many labs are using a variety of different strategies including inserting trans genes that can modulate the innate and adaptive immune response. VSV can also be retargeted by altering its surface glycoprotein (G) or be made replication incompetent by deleting the G protein. Currently, our lab has engineered a series of new recombinant VSVs, incorporating either the murine p53 (mp53), IPS-1, or TRIF transgene. mp53, IPS-1 and TRIF were incorporated into the normal VSV-XN2 genome and mp53 was also incorporated into the mutated VSV-ΔM vector generating VSV-mp53, VSV-IPS-1, VSV-TRIF and VSV-ΔM-mp53. Our data using these new viruses indicate that these viruses preferentially replicate in and kill transformed versus non-transformed cells and efficiently express the transgene. However, despite the ability for VSV-IPS-1 and VSV-TRIF to induce a robust type 1 IFN response, VSV-ΔM-mp53 was the only construct that had reduced toxicity and elicited an increased anti-tumor response against a syngeneic metastatic mammary tumor model. VSV- ΔM-mp53 treatment lead to a reduction in IL-6 and IP-10 production, an increase in tumor specific CD8+ T cells, and immunologic memory against the tumor. Collectively these studies highlight the necessity for additional VSV construct development and the generation of new clinically relevant treatment schema. Advisors/Committee Members: Glen Barber, Ed Harhaj, Eli Gilboa, Jaime Merchan, Joeseph Rosenblatt, Stephen Russell.

Subjects/Keywords: Vesicular Stomatits Virus; p53, oncolytic virus, oncolytic virotherapy

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APA (6^th Edition):

Heiber, J. F. (2011). Characterization and Development of Vesicular Stomatitis Virus For Use as an Oncolytic Vector. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/600

Chicago Manual of Style (16^th Edition):

Heiber, Joshua F. “Characterization and Development of Vesicular Stomatitis Virus For Use as an Oncolytic Vector.” 2011. Doctoral Dissertation, University of Miami. Accessed April 14, 2021. https://scholarlyrepository.miami.edu/oa_dissertations/600.

MLA Handbook (7^th Edition):

Heiber, Joshua F. “Characterization and Development of Vesicular Stomatitis Virus For Use as an Oncolytic Vector.” 2011. Web. 14 Apr 2021.

Vancouver:

Heiber JF. Characterization and Development of Vesicular Stomatitis Virus For Use as an Oncolytic Vector. [Internet] [Doctoral dissertation]. University of Miami; 2011. [cited 2021 Apr 14]. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/600.

Council of Science Editors:

Heiber JF. Characterization and Development of Vesicular Stomatitis Virus For Use as an Oncolytic Vector. [Doctoral Dissertation]. University of Miami; 2011. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/600

University of Oxford

9. Thoma, Clemens Matthias Manuel. Improving intraperitoneal adenovirus virotherapy for ovarian cancer.

Degree: PhD, 2011, University of Oxford

URL: http://ora.ox.ac.uk/objects/uuid:841e4334-f408-4da3-b8e6-1d29350c5304 ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559781

► The use of intraperitoneal (i.p.) adenovirus virotherapy of ovarian cancer is currently limited by insufficient efficacy and high toxicity. Both factors are associated with adenovirus… (more)

▼ The use of intraperitoneal (i.p.) adenovirus virotherapy of ovarian cancer is currently limited by insufficient efficacy and high toxicity. Both factors are associated with adenovirus serotype 5 (Ad5) in this setting and may be serotype-specific. Low levels of uptake receptors (CAR and αV integrins) on ovarian tumour cells and widespread immunity against Ad5 among patients appear to restrict efficacy and intraperitoneal inflammatory responses against Ad5 were among the reasons for the termination of a phase II/III clinical trial in ovarian cancer. This thesis sought to overcome these obstacles by investigating the alternative adenovirus serotypes Ad3 and Ad11. For these viruses lower pre-existing antiviral immunity and utilisation of different uptake receptors have been reported. Furthermore, virus cloaking with novel polymers which could impart enhanced protection from neutralisation was examined. In vitro, wild-type Ad3, Ad5 and Ad11 displayed differential oncolytic activity in a panel of ovarian cancer cell lines which partly correlated to uptake receptor expression and virus internalisation. However, some cell lines displayed lysis resistance in a serotype-specific manner. While the inflammatory response six hours after i.p. administration of Ad11 in CD46-transgenic mice did not differ from Ad5, in long-term studies of repeated administration Ad5 induced significantly more severe pathologic effects in the form of adhesions and liver toxicity than Ad11 or mock-treatment. Oncolysis inhibition assays using malignant exudate samples demonstrated greater neutralisation of Ad3 and Ad5 in comparison to Ad11 at low concentrations of samples. Notably, 10-fold less Ad11 than Ad5 was required for oncolytic efficacy at a sample concentration of 10%. In an ex vivo model of ascites from ovarian cancer patients Ad5 modified with novel polymer formulations achieved at least 50% cell kill in six of eight samples, in contrast to two of eight samples for non-modified Ad5. These data suggest that virotherapy using Ad11 might be advantageous over Ad3 or Ad5. The lack of strong inflammation and the possibility to decrease treatment doses due to less neutralisation of Ad11 might result in considerably improved patient safety. Chemical modification of Ad with novel polymers presents an exciting advancement in overcoming treatment neutralisation in adenovirus virotherapy.

Subjects/Keywords: 616.99465; Oncology; Medical sciences; Tumours; Viruses; Gynaecology; ovarian cancer; oncolytic; oncolytic virotherapy; adenovirus

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APA (6^th Edition):

Thoma, C. M. M. (2011). Improving intraperitoneal adenovirus virotherapy for ovarian cancer. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:841e4334-f408-4da3-b8e6-1d29350c5304 ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559781

Chicago Manual of Style (16^th Edition):

Thoma, Clemens Matthias Manuel. “Improving intraperitoneal adenovirus virotherapy for ovarian cancer.” 2011. Doctoral Dissertation, University of Oxford. Accessed April 14, 2021. http://ora.ox.ac.uk/objects/uuid:841e4334-f408-4da3-b8e6-1d29350c5304 ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559781.

MLA Handbook (7^th Edition):

Thoma, Clemens Matthias Manuel. “Improving intraperitoneal adenovirus virotherapy for ovarian cancer.” 2011. Web. 14 Apr 2021.

Vancouver:

Thoma CMM. Improving intraperitoneal adenovirus virotherapy for ovarian cancer. [Internet] [Doctoral dissertation]. University of Oxford; 2011. [cited 2021 Apr 14]. Available from: http://ora.ox.ac.uk/objects/uuid:841e4334-f408-4da3-b8e6-1d29350c5304 ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559781.

Council of Science Editors:

Thoma CMM. Improving intraperitoneal adenovirus virotherapy for ovarian cancer. [Doctoral Dissertation]. University of Oxford; 2011. Available from: http://ora.ox.ac.uk/objects/uuid:841e4334-f408-4da3-b8e6-1d29350c5304 ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559781

University of Oxford

10. Dyer, Arthur Jack. Exploring the relationship between cancer metabolism and oncolytic adenoviruses.

Degree: PhD, 2021, University of Oxford

URL: http://ora.ox.ac.uk/objects/uuid:3f065eed-9473-4e7b-8806-be34611eb600 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.823620

► Tumour cells exhibiting the Warburg effect rely mostly upon aerobic glycolysis for ATP production and have a notable addiction to anaplerotic use of glutamine for… (more)

▼ Tumour cells exhibiting the Warburg effect rely mostly upon aerobic glycolysis for ATP production and have a notable addiction to anaplerotic use of glutamine for macromolecular synthesis. This strategy maximises cellular biosynthetic potential and provides an attractive anabolic environment for viral infection. Here, we evaluate infection of highly permissive cells (A549 cells) and poorly permissive cells (SKOV3) with wildtype adenoviruses, and the oncolytic chimeric adenovirus enadenotucirev (EnAd) to probe the role of metabolism on the success of oncolytic virotherapy with EnAd. All adenoviruses caused an increase in glucose and glutamine uptake along with increased lactic acid secretion in their host cells, mirroring the canonical Warburg effect phenotype. Through identifying the IC₅₀ of a panel of cancer cells, we identify a correlation showing that cells which rely upon aerobic glycolysis tend to be more permissive to EnAd oncolysis. The virus lifecycle of both wildtype adenoviruses and EnAd were critically dependent on exogenous glutamine. Virus activity in glutamine-free cells was rescued with exogenous membrane-permeable α-ketoglutarate, but not pyruvate or oxaloacetate, suggesting an essential role for reductive carboxylation in glutamine usage. We propose that this unusual glutamine metabolism is beneficial for the production of biosynthetic intermediates, particularly under conditions of hypoxia or decreased cellular respiration as is often seen during adenovirus infection. Counterintuitively, restricting glycolysis using 2-deoxyglucose or by limiting glucose supply strongly improved virus activity in both cell types. Antagonism of glycolysis also boosted EnAd replication and transgene expression within human tumour biopsies, and in xenografted tumours in vivo. We further bolstered this finding through weaning SKOV3 cells off of glucose. This process created a cell line which is highly permissive to EnAd infection and lysis. Finally, we engineered an "armed" EnAd expressing the glycolysis inhibitor TIGAR which was able to lyse cells whilst expressing TIGAR without causing acidification of the media. These findings emphasise the importance of metabolism on productive viral infections which is of particular significance for viruses restricted to replicate in tumours, that already display aberrant metabolic phenotypes.

Subjects/Keywords: Virology; Metabolism; tumour metabolism; Cancer – Immunotherapy; Oncology; oncolytic virotherapy; Gene therapy; oncolytic

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APA (6^th Edition):

Dyer, A. J. (2021). Exploring the relationship between cancer metabolism and oncolytic adenoviruses. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:3f065eed-9473-4e7b-8806-be34611eb600 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.823620

Chicago Manual of Style (16^th Edition):

Dyer, Arthur Jack. “Exploring the relationship between cancer metabolism and oncolytic adenoviruses.” 2021. Doctoral Dissertation, University of Oxford. Accessed April 14, 2021. http://ora.ox.ac.uk/objects/uuid:3f065eed-9473-4e7b-8806-be34611eb600 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.823620.

MLA Handbook (7^th Edition):

Dyer, Arthur Jack. “Exploring the relationship between cancer metabolism and oncolytic adenoviruses.” 2021. Web. 14 Apr 2021.

Vancouver:

Dyer AJ. Exploring the relationship between cancer metabolism and oncolytic adenoviruses. [Internet] [Doctoral dissertation]. University of Oxford; 2021. [cited 2021 Apr 14]. Available from: http://ora.ox.ac.uk/objects/uuid:3f065eed-9473-4e7b-8806-be34611eb600 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.823620.

Council of Science Editors:

Dyer AJ. Exploring the relationship between cancer metabolism and oncolytic adenoviruses. [Doctoral Dissertation]. University of Oxford; 2021. Available from: http://ora.ox.ac.uk/objects/uuid:3f065eed-9473-4e7b-8806-be34611eb600 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.823620

University of Ottawa

11. Allan, Kristina Jean. Enhancing Oncolytic Virotherapy Using Functional Genomic Screening .

Degree: 2018, University of Ottawa

URL: http://hdl.handle.net/10393/37910

At the author’s request, the abstract has been removed due to the confidential nature of the thesis. It will be added once the embargo period has passed.

Subjects/Keywords: oncolytic; virotherapy; cancer; RNAi; vaccinia; screen; high-throughput

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Allan, K. J. (2018). Enhancing Oncolytic Virotherapy Using Functional Genomic Screening . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/37910

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Allan, Kristina Jean. “Enhancing Oncolytic Virotherapy Using Functional Genomic Screening .” 2018. Thesis, University of Ottawa. Accessed April 14, 2021. http://hdl.handle.net/10393/37910.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Allan, Kristina Jean. “Enhancing Oncolytic Virotherapy Using Functional Genomic Screening .” 2018. Web. 14 Apr 2021.

Vancouver:

Allan KJ. Enhancing Oncolytic Virotherapy Using Functional Genomic Screening . [Internet] [Thesis]. University of Ottawa; 2018. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10393/37910.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Allan KJ. Enhancing Oncolytic Virotherapy Using Functional Genomic Screening . [Thesis]. University of Ottawa; 2018. Available from: http://hdl.handle.net/10393/37910

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto

12. Ho, Tiffany Yun-Yee. Designing the Next-generation Oncolytic Vaccinia Virus.

Degree: 2017, University of Toronto

URL: http://hdl.handle.net/1807/77794

►

Many oncolytic viruses (OVs), such as double-deleted vaccina virus (vvDD), are engineered with enhanced tumor-selectivity based on increased cell proliferation in cancer cells. We proposed… (more)

Subjects/Keywords: Cancer therapy; Interferon; Oncolytic virotherapy; Peritoneal Carcinomatosis; Vaccinia Virus; vvDD; 0992

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ho, T. Y. (2017). Designing the Next-generation Oncolytic Vaccinia Virus. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/77794

Chicago Manual of Style (16^th Edition):

Ho, Tiffany Yun-Yee. “Designing the Next-generation Oncolytic Vaccinia Virus.” 2017. Masters Thesis, University of Toronto. Accessed April 14, 2021. http://hdl.handle.net/1807/77794.

MLA Handbook (7^th Edition):

Ho, Tiffany Yun-Yee. “Designing the Next-generation Oncolytic Vaccinia Virus.” 2017. Web. 14 Apr 2021.

Vancouver:

Ho TY. Designing the Next-generation Oncolytic Vaccinia Virus. [Internet] [Masters thesis]. University of Toronto; 2017. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/1807/77794.

Council of Science Editors:

Ho TY. Designing the Next-generation Oncolytic Vaccinia Virus. [Masters Thesis]. University of Toronto; 2017. Available from: http://hdl.handle.net/1807/77794

13. Clarkin, Ryan Gregory. Enhancing Oncolytic Adenovirus Vector Efficacy through Co-expression of the p14 Fusion-associated Small Transmembrane Protein and Adenovirus Death Protein .

Degree: 2018, University of Ottawa

URL: http://hdl.handle.net/10393/38379

► Conditionally-replicating adenoviruses (CRAds) have generally demonstrated only modest therapeutic efficacy in human clinical trials, in part due to their poor ability to spread throughout a… (more)

▼ Conditionally-replicating adenoviruses (CRAds) have generally demonstrated only modest therapeutic efficacy in human clinical trials, in part due to their poor ability to spread throughout a tumor mass. In these studies, I first examined whether inclusion of an intact early region 3 (E3) and the p14 fusion-associated small transmembrane (FAST) protein in a CRAd vector can enhance oncolytic efficacy by improving viral spread. E3 encodes the adenovirus death protein (ADP), which enhances virus progeny release from infected cells, while p14 FAST can allow spread of the virus through cell-cell fusion. I generated viruses with (CRAdRC109) or without (CRAdRC111) an intact E3 region, which encoded the p14 FAST gene between the fiber coding sequence and E4 region of their viral genomes. In the A549 human lung cancer cell line, both CRAdRC109 and CRAdRC111 expressed p14 FAST at very low levels when compared to CRAdFAST, a similar virus that expressed the protein from within the E3 deletion, and thus had a relatively poor ability to mediate cell-cell fusion. Although inclusion of E3/ADP in CRAdRC109 did result in larger plaques and increased virus spread relative to CRAdRC111, neither virus showed improved oncolytic activity relative to CRAdFAST. I subsequently developed CRAdRC116, in which the E3 region of the viral genome was replaced with a bicistronic expression cassette containing the p14 FAST and ADP coding sequences separated by a self-cleaving 2A peptide sequence. This virus co-expressed p14 FAST and ADP and caused extensive cell-cell fusion in A549 cells. However, expression of ADP from CRAdRC116 did not increase cancer cell killing nor virus spread, and thus did not enhance oncolytic efficacy relative to CRAdFAST. These studies suggest that p14 FAST and ADP do not exhibit synergy when co-expressed from a CRAd vector. Future studies should instead focus on combining other methods of improving viral spread in conjunction with expression of ADP or FAST proteins from CRAd.

Subjects/Keywords: Cancer; Adenovirus; Oncolytic; Virotherapy

…improving our ability to treat, and in some cases, cure cancer. 1 1.2. Oncolytic virotherapy… …for cancer treatment Oncolytic virotherapy is an emerging cancer treatment that uses… …field of oncolytic virotherapy was somewhat limited until the 1990s, when researchers began… …x29;. Killing of cancer cells by oncolytic viruses can occur through several different… …genetically engineered oncolytic viruses can be “armed” with therapeutic transgenes to enhance anti…

11 more images…

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APA (6^th Edition):

Clarkin, R. G. (2018). Enhancing Oncolytic Adenovirus Vector Efficacy through Co-expression of the p14 Fusion-associated Small Transmembrane Protein and Adenovirus Death Protein . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/38379

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Clarkin, Ryan Gregory. “Enhancing Oncolytic Adenovirus Vector Efficacy through Co-expression of the p14 Fusion-associated Small Transmembrane Protein and Adenovirus Death Protein .” 2018. Thesis, University of Ottawa. Accessed April 14, 2021. http://hdl.handle.net/10393/38379.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Clarkin, Ryan Gregory. “Enhancing Oncolytic Adenovirus Vector Efficacy through Co-expression of the p14 Fusion-associated Small Transmembrane Protein and Adenovirus Death Protein .” 2018. Web. 14 Apr 2021.

Vancouver:

Clarkin RG. Enhancing Oncolytic Adenovirus Vector Efficacy through Co-expression of the p14 Fusion-associated Small Transmembrane Protein and Adenovirus Death Protein . [Internet] [Thesis]. University of Ottawa; 2018. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10393/38379.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Clarkin RG. Enhancing Oncolytic Adenovirus Vector Efficacy through Co-expression of the p14 Fusion-associated Small Transmembrane Protein and Adenovirus Death Protein . [Thesis]. University of Ottawa; 2018. Available from: http://hdl.handle.net/10393/38379

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Guelph

14. Syed, Zafir. The Combination of Histone Deacetylase Inhibitors and Oncolytic Viruses for the treatment of High-grade Gliomas.

Degree: MS, Department of Pathobiology, 2014, University of Guelph

URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8291

► Survival of patients with high-grade gliomas is dismal. Oncolytic viruses (OV) and histone deacetylase inhibitors (HDIs) represent revolutionary approaches to treating cancers, with minimal toxic… (more)

Subjects/Keywords: oncolytic virotherapy; histone deacetylase inhibitor; brain cancer; glioma

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APA (6^th Edition):

Syed, Z. (2014). The Combination of Histone Deacetylase Inhibitors and Oncolytic Viruses for the treatment of High-grade Gliomas. (Masters Thesis). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8291

Chicago Manual of Style (16^th Edition):

Syed, Zafir. “The Combination of Histone Deacetylase Inhibitors and Oncolytic Viruses for the treatment of High-grade Gliomas.” 2014. Masters Thesis, University of Guelph. Accessed April 14, 2021. https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8291.

MLA Handbook (7^th Edition):

Syed, Zafir. “The Combination of Histone Deacetylase Inhibitors and Oncolytic Viruses for the treatment of High-grade Gliomas.” 2014. Web. 14 Apr 2021.

Vancouver:

Syed Z. The Combination of Histone Deacetylase Inhibitors and Oncolytic Viruses for the treatment of High-grade Gliomas. [Internet] [Masters thesis]. University of Guelph; 2014. [cited 2021 Apr 14]. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8291.

Council of Science Editors:

Syed Z. The Combination of Histone Deacetylase Inhibitors and Oncolytic Viruses for the treatment of High-grade Gliomas. [Masters Thesis]. University of Guelph; 2014. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8291

University of Guelph

15. Ternamian, Christian. Targeting B Cell Acute Lymphoblastic Leukemia with Oncolytic Virotherapy and Histone Deacetylase Inhibition.

Degree: MS, Department of Pathobiology, 2014, University of Guelph

URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8293

► B-cell acute lymphoblastic leukemia (B-ALL) is a hematological disease characterized by the proliferation and extramedullary distribution of malignant B lymphoblasts. Though conventional treatment can be… (more)

Subjects/Keywords: Oncolytic Virotherapy; Histone deacetylase inhibitor; L1210; CD45; Leukemia

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APA (6^th Edition):

Ternamian, C. (2014). Targeting B Cell Acute Lymphoblastic Leukemia with Oncolytic Virotherapy and Histone Deacetylase Inhibition. (Masters Thesis). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8293

Chicago Manual of Style (16^th Edition):

Ternamian, Christian. “Targeting B Cell Acute Lymphoblastic Leukemia with Oncolytic Virotherapy and Histone Deacetylase Inhibition.” 2014. Masters Thesis, University of Guelph. Accessed April 14, 2021. https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8293.

MLA Handbook (7^th Edition):

Ternamian, Christian. “Targeting B Cell Acute Lymphoblastic Leukemia with Oncolytic Virotherapy and Histone Deacetylase Inhibition.” 2014. Web. 14 Apr 2021.

Vancouver:

Ternamian C. Targeting B Cell Acute Lymphoblastic Leukemia with Oncolytic Virotherapy and Histone Deacetylase Inhibition. [Internet] [Masters thesis]. University of Guelph; 2014. [cited 2021 Apr 14]. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8293.

Council of Science Editors:

Ternamian C. Targeting B Cell Acute Lymphoblastic Leukemia with Oncolytic Virotherapy and Histone Deacetylase Inhibition. [Masters Thesis]. University of Guelph; 2014. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8293

University of Oxford

16. Cooper, Lisa May. Bioprocessing of oncolytic group B adenovirus for scalable production.

Degree: PhD, 2014, University of Oxford

URL: https://ora.ox.ac.uk/objects/uuid:bc62bd13-f43f-4d35-8975-7fc341ce209c ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711758

► The central aim of this thesis was to develop strategies to improve the manufacture of the group B chimeric oncolytic adenovirus, ColoAd1, which rapidly kills… (more)

Subjects/Keywords: 616.99; bioprocessing; cancer; adenovirus; oncolytic; replication; virotherapy; metabolism

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APA (6^th Edition):

Cooper, L. M. (2014). Bioprocessing of oncolytic group B adenovirus for scalable production. (Doctoral Dissertation). University of Oxford. Retrieved from https://ora.ox.ac.uk/objects/uuid:bc62bd13-f43f-4d35-8975-7fc341ce209c ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711758

Chicago Manual of Style (16^th Edition):

Cooper, Lisa May. “Bioprocessing of oncolytic group B adenovirus for scalable production.” 2014. Doctoral Dissertation, University of Oxford. Accessed April 14, 2021. https://ora.ox.ac.uk/objects/uuid:bc62bd13-f43f-4d35-8975-7fc341ce209c ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711758.

MLA Handbook (7^th Edition):

Cooper, Lisa May. “Bioprocessing of oncolytic group B adenovirus for scalable production.” 2014. Web. 14 Apr 2021.

Vancouver:

Cooper LM. Bioprocessing of oncolytic group B adenovirus for scalable production. [Internet] [Doctoral dissertation]. University of Oxford; 2014. [cited 2021 Apr 14]. Available from: https://ora.ox.ac.uk/objects/uuid:bc62bd13-f43f-4d35-8975-7fc341ce209c ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711758.

Council of Science Editors:

Cooper LM. Bioprocessing of oncolytic group B adenovirus for scalable production. [Doctoral Dissertation]. University of Oxford; 2014. Available from: https://ora.ox.ac.uk/objects/uuid:bc62bd13-f43f-4d35-8975-7fc341ce209c ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711758

University of Adelaide

17. Singleton, Eve Victoria. Sterility and immunogenicity of gamma-irradiated respiratory viruses.

Degree: 2020, University of Adelaide

URL: http://hdl.handle.net/2440/128819

► Gamma (γ)-radiation is a method commonly applied to sterilise pathogens in the biomedical, food and pharmaceutical industries. γ-radiation inactivates pathogens by causing irreparable damage to… (more)

▼ Gamma (γ)-radiation is a method commonly applied to sterilise pathogens in the biomedical, food and pharmaceutical industries. γ-radiation inactivates pathogens by causing irreparable damage to genomes to prevent replication. However, proteins and other antigenic structures are left mostly intact. In recent years there has been increasing advocacy for highly immunogenic g-irradiated vaccines, several of which are currently in clinical or pre-clinical trials. Importantly, various methods of mathematical modelling and sterility testing are employed to ensure the safety of a given preparation. However, these methods are designed for materials with a low bioburden, such as food and pharmaceuticals. Consequently, current methods may not be reliable or applicable to estimate the irradiation dose required to sterilise microbiological preparations for vaccine purposes, where bioburden is deliberately high. In this study, I investigated different methods of modelling sterility and developed a new formula for calculating sterilising doses that is highly applicable to viruses and bacteria. Our research group has developed a whole-inactivated influenza A virus (IAV) vaccine using γ-radiation (γ-Flu). IAV presents a constant pandemic threat due to the mutagenic nature of the virus and the inadequacy of current vaccines to protect against emerging strains. Previous research has demonstrated the ability of γ-Flu to protect against not only vaccine-included strains but emerging strains as well. In this study, I compared γ-Flu irradiated at different temperatures and doses to meet internationally accepted sterility assurance levels. I found that, when using sterilising doses, the structural integrity and vaccine efficacy was well maintained regardless of irradiation temperature. In fact, using a higher temperature and lower radiation dose induced higher neutralising antibody responses and more effective cytotoxic T cell responses. These data provided new insights into optimal irradiation conditions as previously using frozen irradiation was considered the superior irradiation temperature. These concepts related to preparing γ-irradiated vaccines were applied to the development of a novel vaccine against Newcastle disease virus (NDV). NDV is an important poultry pathogen that is associated with widespread livestock losses and a large economic burden. Current vaccines are available but have limited efficacy so there exists a need for alternative NDV vaccines. In this study, NDV was inactivated by γ-irradiation and structural integrity was tested. I found overall virion structure and protein function of γ-NDV to be well maintained, however surprisingly I did not detect neutralising antibody responses after treatment in mice. Interestingly, previous studies from our group have demonstrated the ability of γ-Flu to adjuvant other γ-irradiated vaccines. In the current study, I expanded on the broader applicability of γ-Flu as an adjuvant by showing that γ-Flu can adjuvant the poorly immunogenic keyhole limpet hemocyanin. However, γ-Flu and… Advisors/Committee Members: Alsharifi, Mohammed (advisor), Beard, Michael (advisor), Hemmatzadeh, Farhid (advisor), Davies, Justin (advisor), School of Biological Sciences (school).

Subjects/Keywords: Gamma radiation; Influenza A virus; Newcastle disease virus; vaccine; oncolytic virotherapy

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APA (6^th Edition):

Singleton, E. V. (2020). Sterility and immunogenicity of gamma-irradiated respiratory viruses. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/128819

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Singleton, Eve Victoria. “Sterility and immunogenicity of gamma-irradiated respiratory viruses.” 2020. Thesis, University of Adelaide. Accessed April 14, 2021. http://hdl.handle.net/2440/128819.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Singleton, Eve Victoria. “Sterility and immunogenicity of gamma-irradiated respiratory viruses.” 2020. Web. 14 Apr 2021.

Vancouver:

Singleton EV. Sterility and immunogenicity of gamma-irradiated respiratory viruses. [Internet] [Thesis]. University of Adelaide; 2020. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2440/128819.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Singleton EV. Sterility and immunogenicity of gamma-irradiated respiratory viruses. [Thesis]. University of Adelaide; 2020. Available from: http://hdl.handle.net/2440/128819

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Urbana-Champaign

18. Thomas, Diana L. Evaluation of Adoptive T Cell Therapy and Oncolytic Virotherapy for Treatment of Brain Tumors.

Degree: PhD, 0323, 2011, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/18568

► Adoptive immunotherapy and oncolytic virotherapy are two promising strategies for treating primary and metastatic malignant brain tumors. We demonstrate the ability of adoptively transferred tumor-specific… (more)

▼ Adoptive immunotherapy and oncolytic virotherapy are two promising strategies for treating primary and metastatic malignant brain tumors. We demonstrate the ability of adoptively transferred tumor-specific T cells to rapidly mediate the clearance of established brain tumors in several mouse models. Similar to the clinical situation, tumor recurrences are frequent and result from immune editing of tumors. T cells can eliminate antigen-expressing tumor cells but are not effective against antigen loss variant (ALV) cancer cells that multiply and repopulate a tumor. We show that the level of tumor antigen present affects the success of adoptive T cell therapy. When high levels of antigen are present, tumor stromal cells such as microglia and macrophages present tumor peptide on their surface. As a result, T cells directly eliminate cancer cells and cross-presenting stromal cells and indirectly eliminate ALV cells. We were able to show the first direct evidence of tumor antigen cross-presentation by CD11b+ stromal cells in the brain using soluble, high-affinity T cell receptor monomers. Strategies that target brain tumor stroma or increase antigen shedding from tumor cells leading to increased crosspresentation by stromal cells may improve the clinical success of T cell adoptive therapies. We evaluated one potential strategy to complement adoptive T cell therapy by characterizing the oncolytic effects of myxoma virus (MYXV) in a syngeneic mouse brain tumor model of metastatic melanoma. MYXV is a rabbit poxvirus with strict species tropism for European rabbits. MYXV can also infect mouse and human cancer cell lines due to signaling defects in innate antiviral mechanisms and hyperphosphorylation of Akt. MYXV kills B16.SIY melanoma cells in vitro, and intratumoral injection of virus leads to robust, selective and transient infection of the tumor. We observed that virus treatment recruits innate immune cells iii to the tumor, induces TNFα and IFNβ production in the brain, and results in limited oncolytic effects in vivo. To overcome this, we evaluated the safety and efficacy of co-administering 2C T cells, MYXV, and neutralizing antibodies against IFNβ. Mice that received the triple combination therapy survived significantly longer with no apparent side effects, but eventually relapsed. Based on these findings, methods to enhance viral replication in the tumor and limit immune clearance of the virus will be pursued. We conclude that myxoma virus should be further explored as a vector for transient delivery of therapeutic genes to a tumor to enhance T cell responses. Advisors/Committee Members: Roy, Edward J. (advisor), Roy, Edward J. (Committee Chair), Kranz, David M. (committee member), MacNeill, Amy L. (committee member), Ceman, Stephanie S. (committee member), George, Julia M. (committee member).

Subjects/Keywords: brain tumors; immunotherapy; oncolytic virotherapy; Melanoma; Adoptive T Cell Therapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Thomas, D. L. (2011). Evaluation of Adoptive T Cell Therapy and Oncolytic Virotherapy for Treatment of Brain Tumors. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/18568

Chicago Manual of Style (16^th Edition):

Thomas, Diana L. “Evaluation of Adoptive T Cell Therapy and Oncolytic Virotherapy for Treatment of Brain Tumors.” 2011. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/18568.

MLA Handbook (7^th Edition):

Thomas, Diana L. “Evaluation of Adoptive T Cell Therapy and Oncolytic Virotherapy for Treatment of Brain Tumors.” 2011. Web. 14 Apr 2021.

Vancouver:

Thomas DL. Evaluation of Adoptive T Cell Therapy and Oncolytic Virotherapy for Treatment of Brain Tumors. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2011. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/18568.

Council of Science Editors:

Thomas DL. Evaluation of Adoptive T Cell Therapy and Oncolytic Virotherapy for Treatment of Brain Tumors. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2011. Available from: http://hdl.handle.net/2142/18568

Arizona State University

19. Kasimsetty, Aradhana. Characterization of the Role of Necroptosis for Oncolytic Vaccinia Efficacy.

Degree: Biology, 2020, Arizona State University

URL: http://repository.asu.edu/items/57343

► Since the molecular biology revolution in the 1980s, ease of gene editing had led to the resurgence of Oncolytic Virotherapy. Countless viruses have been engineered… (more)

Subjects/Keywords: Virology; Oncology; Immunology; E3L; Necroptosis; Oncolytic Virotherapy; RIP3; RIP3K; Vaccinia Virus

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APA (6^th Edition):

Kasimsetty, A. (2020). Characterization of the Role of Necroptosis for Oncolytic Vaccinia Efficacy. (Masters Thesis). Arizona State University. Retrieved from http://repository.asu.edu/items/57343

Chicago Manual of Style (16^th Edition):

Kasimsetty, Aradhana. “Characterization of the Role of Necroptosis for Oncolytic Vaccinia Efficacy.” 2020. Masters Thesis, Arizona State University. Accessed April 14, 2021. http://repository.asu.edu/items/57343.

MLA Handbook (7^th Edition):

Kasimsetty, Aradhana. “Characterization of the Role of Necroptosis for Oncolytic Vaccinia Efficacy.” 2020. Web. 14 Apr 2021.

Vancouver:

Kasimsetty A. Characterization of the Role of Necroptosis for Oncolytic Vaccinia Efficacy. [Internet] [Masters thesis]. Arizona State University; 2020. [cited 2021 Apr 14]. Available from: http://repository.asu.edu/items/57343.

Council of Science Editors:

Kasimsetty A. Characterization of the Role of Necroptosis for Oncolytic Vaccinia Efficacy. [Masters Thesis]. Arizona State University; 2020. Available from: http://repository.asu.edu/items/57343

INP Toulouse

20. Ricordel, Marine. Sélection, Génération et Amélioration de Poxvirus Oncolytiques par Génie Génétique et Evolution Dirigée : Selection, generation and improvement of oncolytic poxviruses with viral engineering and directed evolution.

Degree: Docteur es, Pathologie, Toxicologie, Génétique et Nutrition, 2018, INP Toulouse

URL: http://www.theses.fr/2018INPT0010

►

Les virus oncolytiques sont une nouvelle classe d’agents thérapeutiques pouvant être une alternative au traitement des cancers. Plusieurs virus oncolytiques sont actuellement développés en clinique,… (more)

▼

Les virus oncolytiques sont une nouvelle classe d’agents thérapeutiques pouvant être une alternative au traitement des cancers. Plusieurs virus oncolytiques sont actuellement développés en clinique, néanmoins de nombreuses améliorations sont à apporter afin de créer une nouvelle classe de virus plus efficaces et moins toxiques. Le premier objectif de cette thèse a été d’améliorer la spécificité tumorale du virus de la vaccine via le ciblage de l’antigène MUC1 présenté à la surface des cellules tumorales. Pour cela un virus recombinant présentant à sa surface un fragment d’anticorps (scFv) dirigé contre l’antigène tumoral MUC1 a été construit et produit. Les tests in vitro n’ont toutefois pas permis de mettre en évidence un ciblage spécifique du virus recombinant. Un deuxième aspect de cette thèse a été de tester le potentiel oncolytique de virus de la famille des Poxviridae. Durant ce travail de thèse, les capacités oncolytiques de douze poxvirus, appartenant à 8 genres différents, ont été étudiés. Leurs effets sur la prolifération de cellules cancéreuses humaines ont été évalués. Les virus caractérisés par un effet oncolytique élevé ont été, par la suite, modifiés et armés par ingénierie virale afin d’augmenter leur efficacité. La dernière partie de cette thèse a été consacrée à la génération et la sélection de virus chimériques basées sur la méthode d’évolution dirigée. Cette méthode est utilisée pour mimer le processus naturel de sélection évolutif. Appliqué à la virothérapie oncolytique, ce procédé nous a permis de générer un nouveau virus oncolytique chimérique caractérisé par un potentiel anti-cancéreux amélioré. En résumé, cette thèse a permis, par des techniques d’ingénierie virale, par un criblage de nouveaux virus et par la méthode d’évolution dirigée, de créer et de sélectionner une nouvelle génération de poxvirus oncolytiques présentant une activité thérapeutique accrue avec un profil de toxicité atténué et pouvant être utilisés dans diverses indications thérapeutiques.

Oncolytiques viruses are a new class of therpeutic agents which could be an alternative for cancer treatment. Currently, several oncolytic viruses are evaluated in clinical trial, nevertheless improvements are needed to create a new class of more efficiente and less toxic viruses. The first objective of this thesis was to improved the vaccinia virus specificity through the targeting of the tumor-associated antigen MUC1. To address this goal, a recombinant virus expressing an scFv targeting the MUC1-protein was engineered and produced. However, in vitro, the demonstration of a specific targeting by the recombinant virus was not possible. A second aspect of this thesis work was to evaluate the oncolytic potential of Poxviridae family viruses. Oncolytic capacities of twelve viruses, belonging to eight genera, were evaluated. Their impact on human cancer cells was tested. In order to increase their efficacity, viruses with the highest oncolytic capacities were then modified and armed by genetic engineering. The third part of this work was…

Advisors/Committee Members: Bertagnoli, Stéphane (thesis director), Camus, Christelle (thesis director).

Subjects/Keywords: Poxvirus; Virothérapie oncolytique; Tropisme tumoral; Evolution dirigée; Poxviruses; Oncolytic virotherapy; Tropism modification; Directed evolution

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ricordel, M. (2018). Sélection, Génération et Amélioration de Poxvirus Oncolytiques par Génie Génétique et Evolution Dirigée : Selection, generation and improvement of oncolytic poxviruses with viral engineering and directed evolution. (Doctoral Dissertation). INP Toulouse. Retrieved from http://www.theses.fr/2018INPT0010

Chicago Manual of Style (16^th Edition):

Ricordel, Marine. “Sélection, Génération et Amélioration de Poxvirus Oncolytiques par Génie Génétique et Evolution Dirigée : Selection, generation and improvement of oncolytic poxviruses with viral engineering and directed evolution.” 2018. Doctoral Dissertation, INP Toulouse. Accessed April 14, 2021. http://www.theses.fr/2018INPT0010.

MLA Handbook (7^th Edition):

Ricordel, Marine. “Sélection, Génération et Amélioration de Poxvirus Oncolytiques par Génie Génétique et Evolution Dirigée : Selection, generation and improvement of oncolytic poxviruses with viral engineering and directed evolution.” 2018. Web. 14 Apr 2021.

Vancouver:

Ricordel M. Sélection, Génération et Amélioration de Poxvirus Oncolytiques par Génie Génétique et Evolution Dirigée : Selection, generation and improvement of oncolytic poxviruses with viral engineering and directed evolution. [Internet] [Doctoral dissertation]. INP Toulouse; 2018. [cited 2021 Apr 14]. Available from: http://www.theses.fr/2018INPT0010.

Council of Science Editors:

Ricordel M. Sélection, Génération et Amélioration de Poxvirus Oncolytiques par Génie Génétique et Evolution Dirigée : Selection, generation and improvement of oncolytic poxviruses with viral engineering and directed evolution. [Doctoral Dissertation]. INP Toulouse; 2018. Available from: http://www.theses.fr/2018INPT0010

21. Betancourt, Dillon M. Vesicular Stomatitis Virus is a Malleable Oncolytic Vector for the Treatment of Various Malignancies.

Degree: PhD, Microbiology and Immunology (Medicine), 2017, University of Miami

URL: https://scholarlyrepository.miami.edu/oa_dissertations/1873

► Oncolytic virotherapy is an exciting field that is currently generating a significant amount of interest. Several viruses have recently been approved for clinical use… (more)

▼ Oncolytic virotherapy is an exciting field that is currently generating a significant amount of interest. Several viruses have recently been approved for clinical use and there are many more in clinical trials awaiting approval. Vesicular Stomatitis Virus (VSV) has performed remarkably well in many preclinical studies and several strains have entered clinical trials across the world. VSV is a negative strand ssRNA virus in the Rhabdoviridae family and mainly infects livestock which produce sores on the mucus membranes. VSV infection in humans is extremely rare and most often asymptomatic due to its inability to overcome the innate and adaptive immune response of healthy individuals. However, upon infection of many types of cancerous cells VSV displays rapid growth kinetics and significant oncolytic potential due to defects in innate immune and translational control pathways commonly seen in cancer cells. VSV is of significant research interest partly due to its simple genome that is highly malleable. The entire 11kb genome has been cloned into a cDNA plasmid and the insertion and deletion of different genes allows for a highly customizable virus that researchers can take advantage. One such modification in our lab is the replacement of the VSV glycoprotein with a fusion protein created using domains of HIV-1 gp160 and VSV-G. The fusion protein dubbed gp160G was properly incorporated into VSV virions and successfully altered the tropism of the virus. VSV-gp160G was selective for CD4+ cells and induced significant amounts of syncytia and apoptosis during infection of Hela CD4+ and adult T cell leukemia (ATL) cells. When used as a therapeutic in an ATL mouse model, VSV-gp160G improved survival time of tumor bearing mice and significantly reduced the onset of metastasis. The success of VSV-gp160G as a targeted therapy in ATL mouse models warrants further study as the virus could be an important therapeutic option to treat ATL in the clinic. Advisors/Committee Members: Glen N. Barber, XiangXi Xu, Samita Andreansky, Enrique A. Mesri, Jaime Merchan, Balveen Kaur.

Subjects/Keywords: VSV; cancer; oncolytic virotherapy; ATL

…ANCIENT DISEASE TO MODERN TIMES �� …. 1 2 ONCOLYTIC VIROTHERAPY: RECRUITING VIRUSES TO… …ONCOLYTIC VECTOR ��….......................................................................... 55… …4 RETARGETING ONCOLYTIC VESICULAR STOMATITIS VIRUS TO HUMAN T-CELL LYMPHOTROPIC VIRUS… …VSV-gp160G remains potently oncolytic page 88 Figure 4.3 VSV-gp160G is specific for…

15 more images…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Betancourt, D. M. (2017). Vesicular Stomatitis Virus is a Malleable Oncolytic Vector for the Treatment of Various Malignancies. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/1873

Chicago Manual of Style (16^th Edition):

Betancourt, Dillon M. “Vesicular Stomatitis Virus is a Malleable Oncolytic Vector for the Treatment of Various Malignancies.” 2017. Doctoral Dissertation, University of Miami. Accessed April 14, 2021. https://scholarlyrepository.miami.edu/oa_dissertations/1873.

MLA Handbook (7^th Edition):

Betancourt, Dillon M. “Vesicular Stomatitis Virus is a Malleable Oncolytic Vector for the Treatment of Various Malignancies.” 2017. Web. 14 Apr 2021.

Vancouver:

Betancourt DM. Vesicular Stomatitis Virus is a Malleable Oncolytic Vector for the Treatment of Various Malignancies. [Internet] [Doctoral dissertation]. University of Miami; 2017. [cited 2021 Apr 14]. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/1873.

Council of Science Editors:

Betancourt DM. Vesicular Stomatitis Virus is a Malleable Oncolytic Vector for the Treatment of Various Malignancies. [Doctoral Dissertation]. University of Miami; 2017. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/1873

University of Oxford

22. Cawood, Ryan. Liver specific microRNA control of adenovirus serotype five.

Degree: PhD, 2011, University of Oxford

URL: http://ora.ox.ac.uk/objects/uuid:d97d80b5-6272-4aab-b555-d03d0016eeff ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.543557

► MicroRNAs are small non-coding RNA molecules that regulate mRNA translation by binding to complementary sequences usually within the 3’ un-translated region (UTR). By inserting four… (more)

▼ MicroRNAs are small non-coding RNA molecules that regulate mRNA translation by binding to complementary sequences usually within the 3’ un-translated region (UTR). By inserting four perfectly complementary binding sites for the hepatic specific microRNA mir122 into the 3’ UTR of adenovirus wild type 5 (Ad5 WT) E1A mRNA I show that the acute liver toxicity caused by Ad5 WT in mice can be significantly reduced. This virus, termed Ad5-mir122, is a promising virotherapy candidate and causes no obvious liver pathology whilst maintaining Ad5 WT replication in mir122 negative cells. Data shows that repeat intravenous administration of Ad5-mir122 (2x1010vp) to HepG2 tumour bearing mice mediated significant anti-cancer efficacy. RT-QPCR for E1A mRNA demonstrated a 29-fold reduction when compared to Ad5 WT in murine liver whilst western blot confirmed that all E1A protein variants were knocked down. Viral genomic replication was also reduced in mouse liver by 25-fold compared to Ad5 WT. This control of virus activity reduced alanine and aspartate transaminase release by >15-fold and histological analysis showed little to no pathology in Ad5-mir122 infected livers. Measurement of mature mir122 levels in Ad5-mir122 infected livers by RT-QPCR showed that the quantity of mir122 remained unaffected at therapeutic doses. Complete genome mRNA array profiling of infected livers showed that the transcript levels of >3900 different mRNAs were changed more than 2-fold following Ad5 WT infection whilst less than 600 were changed by Ad5-mir122. A non-replicating control adenovirus vector altered >550 mRNAs. No known mir122 target mRNAs were affected following infection with Ad5-mir122. Western blot analysis of a known mir122 regulated target (Aldolase A) confirmed these results, demonstrating no change in protein level despite infection with Ad5-mir122. These data combined demonstrate that the exploitation of microRNA mir122 regulation to control adenovirus replication is a safe method of control and does not alter the endogenous level or activity of the microRNA or its endogenous mRNA targets. Ad5-mir122 is a potent anti-cancer agent that replicates to wild-type levels in microRNA mir122 negative cells but is specifically and safely attenuated in hepatocytes.

Subjects/Keywords: 615.1; Gene medicine; Medical Sciences; Biology (medical sciences); Oncology; Viruses; Biology; microRNA; virotherapy; oncolytic; adenovirus

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cawood, R. (2011). Liver specific microRNA control of adenovirus serotype five. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:d97d80b5-6272-4aab-b555-d03d0016eeff ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.543557

Chicago Manual of Style (16^th Edition):

Cawood, Ryan. “Liver specific microRNA control of adenovirus serotype five.” 2011. Doctoral Dissertation, University of Oxford. Accessed April 14, 2021. http://ora.ox.ac.uk/objects/uuid:d97d80b5-6272-4aab-b555-d03d0016eeff ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.543557.

MLA Handbook (7^th Edition):

Cawood, Ryan. “Liver specific microRNA control of adenovirus serotype five.” 2011. Web. 14 Apr 2021.

Vancouver:

Cawood R. Liver specific microRNA control of adenovirus serotype five. [Internet] [Doctoral dissertation]. University of Oxford; 2011. [cited 2021 Apr 14]. Available from: http://ora.ox.ac.uk/objects/uuid:d97d80b5-6272-4aab-b555-d03d0016eeff ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.543557.

Council of Science Editors:

Cawood R. Liver specific microRNA control of adenovirus serotype five. [Doctoral Dissertation]. University of Oxford; 2011. Available from: http://ora.ox.ac.uk/objects/uuid:d97d80b5-6272-4aab-b555-d03d0016eeff ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.543557

Stellenbosch University

23. Winnie Wanja, Chabaari. Intracellular and immune-response delays effects on the interation between tumor cells, oncolytic viruses and the immune system.

Degree: MSc, Mathematical Sciences, 2019, Stellenbosch University

URL: http://hdl.handle.net/10019.1/106928

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ENGLISH ABSTRACT: Lately, oncolytic viruses have been used to mitigate cancer as they lyse tumor cells whilst leaving normal cells largely unharmed (as opposed to… (more)

▼

ENGLISH ABSTRACT: Lately, oncolytic viruses have been used to mitigate cancer as they lyse tumor cells whilst leaving normal cells largely unharmed (as opposed to many other forms of cancer treatment). The oncolytic effect depends on both viral replication ability and immune response type induced by said replication. A major challenge posed by this therapy is any potential delay that can occur during viral replication, combined with a fast immune response. For this project, we will investigate possible trade-offs of the interactions, with particular focus on the effect(s) of delay.We will extend recently published mathematical models on virotherapy by taking into account the simultaneous effect of the delay and considering various forms of virus-cell infections. We perform stability analysis with the delay and run numerical simulations to confirm the mathematical findings and see how well this model would fit data or whether by the introduction of the delay terms, we improve the fit of the data. Eventually, we derive an explicit formula for the trade-off between the two delays that leads to tumor eradication. One of the main findings is the occurrence of a delay-induced Hopf bifurcation, indicative of tumor relapse which is a confirmation of other previous cancer virotherapy mathematical models.

AFRIKAANSE OPSOMMING: Onkolitiese virusse word die afgelope tyd gebruik om kanker te versag, aangesien hulle tumorselle lig, terwyl normale selle grootliks ongedeerd bly (in teenstelling met baie ander vorme van kankerbehandeling). Die onkolitiese effek is afhanklik van sowel die virale replikasievermoë as die immuun-re-sponse tipe wat deur genoemde replikasie veroorsaak word. 'n Groot uitdaging wat hierdie terapie inhou, is die potensiële vertraging wat tydens virusreplikasie kan voorkom, gekombineer met 'n vinnige immuunreaksie. Vir hierdie projek ondersoek ons moontlike inruilings van die interaksies, veral met die oog op die gevolge van vertraging. Ons brei wiskundige modelle oor viroterapie wat onlangs gepubliseer is, uit deur die gelyktydige effek van die vertraging en die oorweging van verskillende vorme van virusselinfeksies in ag te neem. Ons doen stabiliteitsanalise met die vertraging en voer numeriese simulasies uit om die wiskundige bevindings te bevestig en te bepaal hoe goed hierdie model by die data sou pas, of deur die inwerkingtreding van die vertragingsterme die pas van die data te verbeter. Uiteindelik verkry ons 'n eksplisiete formule vir die verhandeling tussen die twee vertragings wat lei tot die uitwissing van gewasse. Een van die belangrikste bevindings is die voorkoms van 'n vertraging-geïnduseerde Hopf-bifurkasie, wat 'n aanduiding is van tumorterugval, wat die bevestiging is van ander vorige wiskundige modelle vir kankerviroterapie.

Masters

Advisors/Committee Members: Pulliam, Juliet R. C., Ouifki, Rachid, Eladdadi, Amina, Stellenbosch University. Faculty of Science. Dept. of Mathematical Sciences.

Subjects/Keywords: Oncolytic virotherapy – Mathematical models; Delay differential equations; MATLAB; Immuno response – Simulation methods; Cancer – Treatment – Mathematical models; Virusses – Therapeutic use; Virotherapy – Mathematical models

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Winnie Wanja, C. (2019). Intracellular and immune-response delays effects on the interation between tumor cells, oncolytic viruses and the immune system. (Masters Thesis). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/106928

Chicago Manual of Style (16^th Edition):

Winnie Wanja, Chabaari. “Intracellular and immune-response delays effects on the interation between tumor cells, oncolytic viruses and the immune system.” 2019. Masters Thesis, Stellenbosch University. Accessed April 14, 2021. http://hdl.handle.net/10019.1/106928.

MLA Handbook (7^th Edition):

Winnie Wanja, Chabaari. “Intracellular and immune-response delays effects on the interation between tumor cells, oncolytic viruses and the immune system.” 2019. Web. 14 Apr 2021.

Vancouver:

Winnie Wanja C. Intracellular and immune-response delays effects on the interation between tumor cells, oncolytic viruses and the immune system. [Internet] [Masters thesis]. Stellenbosch University; 2019. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10019.1/106928.

Council of Science Editors:

Winnie Wanja C. Intracellular and immune-response delays effects on the interation between tumor cells, oncolytic viruses and the immune system. [Masters Thesis]. Stellenbosch University; 2019. Available from: http://hdl.handle.net/10019.1/106928

24. Saloura, Vassiliki. Ο ρόλος των ιών ως φορέων στη γονιδιακή θεραπεία του κακοήθους μεσοθηλιώματος.

Degree: 2017, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)

URL: http://hdl.handle.net/10442/hedi/42194

► The results of the described research projects support that the oncolytic virus VSV.IFN-β manifests remarkable anticancer effects against mesothelioma cancer cells and this is mediated… (more)

▼ The results of the described research projects support that the oncolytic virus VSV.IFN-β manifests remarkable anticancer effects against mesothelioma cancer cells and this is mediated not only through direct lysis of cancer cells, but also through the induction of CD8+ T-cell mediated anticancer immunity. Furthermore, immunocompetent mice that were cured and remained cancer free for more than 6 months after treatment of heterotopic subcutaneous mouse mesothelioma flank tumors with VSV.mIFN-β did not develop new flank tumors after reexposure to subcutaneous injections with the same mouse mesothelioma cells, indicating the development of anticancer “immune memory”. These results support the translation of VSV.IFN-β in clinical trials as a novel therapeutic approach for patients with malignant pleural mesothelioma. However, the efficacy of VSV.IFN-β depends on the functionality of the type I IFN pathways, an observation which was expected if one considers the exquisite sensitivity of VSV to the antiviral functions of type I IFNs. Although a large percentage of cancer cells have evolutionarily favored the deactivation of type I IFN pathways due to their antiproliferative effects in cancer growth, the presence of some cancer cells with “active” type I IFN pathways pose an inherent mechanism of resistance to the oncolytic effects of VSV. With this in mind, it is necessary to develop personalized therapeutic strategies, i.e. immunohistochemistry for biomarkers indicative of “active” or “inactive” type I IFN pathways, in order to select patients who have higher chances of responding to the oncolytic effects of VSV. One of the main reasons for the genetic engineering of VSV to express IFN-β is the improved safety of it in case of infection of normal cells by tes virus; in this case, the expression of IFN-β would be expected to enhance the antiviral response of normal cells to the virus, preventing the replication of the virus and thus cell death. Although VSV.mIFN-β did not induce significant side effects and was very well tolerated at the treatment doses administered to immunocompetent mice, neurotoxic complications were observed in the immunodeficient mice treated with VSV.hIFN-β and VSV.GFP. Other studies have also demonstrated neurotoxicity of wild-type VSV in mice. These observations have raised doubts about the safety of the administration of this virus in patients with malignant pleural mesothelioma who could become immunosuppressed in the context of their malignancy or their treatment with chemotherapy. Hence, for the therapeutic administration of this virus the use of modified, nontoxic, attenuated viral strains is necessary or one should consider the local rather than systemic administration of this virus. Another very important obstacle in the clinical application of VSV, as well as of other oncolytic viruses, is the induction of neutralizing antibodies that inactivate the virus, especially after its systemic administration. Strategies that could be applied to reduce the immunogenicity of this virus…

Subjects/Keywords: κακόηθες μεσοθηλίωμα; Γονιδιακή θεραπεία; ογκολυτική ιοθεραπεία; ιός θυλακιώδους στοματίτιδας; Malignant mesothelioma; Gene therapy; Oncolytic virotherapy; Vesicular stomatitis virus

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Saloura, V. (2017). Ο ρόλος των ιών ως φορέων στη γονιδιακή θεραπεία του κακοήθους μεσοθηλιώματος. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/42194

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Saloura, Vassiliki. “Ο ρόλος των ιών ως φορέων στη γονιδιακή θεραπεία του κακοήθους μεσοθηλιώματος.” 2017. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed April 14, 2021. http://hdl.handle.net/10442/hedi/42194.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Saloura, Vassiliki. “Ο ρόλος των ιών ως φορέων στη γονιδιακή θεραπεία του κακοήθους μεσοθηλιώματος.” 2017. Web. 14 Apr 2021.

Vancouver:

Saloura V. Ο ρόλος των ιών ως φορέων στη γονιδιακή θεραπεία του κακοήθους μεσοθηλιώματος. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2017. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10442/hedi/42194.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Saloura V. Ο ρόλος των ιών ως φορέων στη γονιδιακή θεραπεία του κακοήθους μεσοθηλιώματος. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2017. Available from: http://hdl.handle.net/10442/hedi/42194

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Stellenbosch University

25. Mahasa, Khaphetsi Joseph. Mathematical Modelling of Tumour-Immune Interactions and Cancer Therapy.

Degree: PhD, Mathematical Sciences, 2017, Stellenbosch University

URL: http://hdl.handle.net/10019.1/102597

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ENGLISH ABSTRACT : The immune system plays a key role against the development and progression of tumor cells mainly because of its capability of recognizing… (more)

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ENGLISH ABSTRACT : The immune system plays a key role against the development and progression of tumor cells mainly because of its capability of recognizing and destroying cancerous cells. While incredible research efforts have been made over the past decades to decipher the complexity of the tumor-immnue interactions, there is still a lack of a definite and complete picture of these interactions. This may be attributed to the fact that tumor cells develop intricate mechanisms to evade detection and control by the immune system and resist treatments. Although this has been attributed to tumor escape from the immune system, no quantitative studies have been made to precisely characterize key tumor evasion mechanisms from immune surveillance. There is a growing need for new modeling approaches that take into account the complexity of immune system response and/or tumor escape mechanisms, and the recent advances in cancer therapy. This lack has motivated the work in this thesis. We focused our research on addressing the following three scientific questions: (1) How do tumors evolve by escaping immune surveillance? (2) How can oncolytic virus infection of some normal cells in the vicinity of tumor cells enhance oncolytic virotherapy? (3) How can the use of cell carriers for the delivery of oncolytic virus particles to tumor sites affect the outcomes of oncolytic virotherapy in the presence of active immune response? To address these major questions, we have devised three novel mathematical models to study the behaviour of tumor cells following their interactions with key cytotoxic immune cells and oncolytic viruses. The results herein this thesis show the development of immunoresistant phenotype by tumor cells to effectively evade the immune system. This thesis supports the natural killer (NK) cell-based immunotherapeutic approaches that are aimed at enhancing the immune surveillance of tumors. Our work also highlights an interesting possibility of infecting some normal cells in the vicinity of tumor cells to increase the oncolytic infectious titers within tumor microenvironment. Additionally, our findings provide pertinent information on how the use of certain cell carriers may enhance oncolytic virotherapy in the presence of effective immune response within the tumor microenvironment.

AFRIKAANSE OPSOMMING : Die immuunstelsel speel ’n sleutelrol om die ontwikkeling en groei van tumor selle teen te werk, hoofsaaklik as gevolg van die vermo¨e om kanker selle te herken en te vernietig. Terwyl ongelooflike navorsing oor die afgelope dekades gedoen is om die kompleksiteit van die tumor-immuun interaksies te ontleed, is daar nog nie ’n definitiewe en volledige beeld van hierdie interaksies nie. Dit kan toegeskryf word aan die feit dat tumorselle ingewikkelde meganismes ontwikkel om opsporing en beheer deur die immuunstelsel te ontduik en behandelings te weerstaan. Alhoewel dit toegeskryf word aan tumors wat van die immuunstelsel onsnap, is geen kwantitatiewe studies gedoen om die belangrikste…

Advisors/Committee Members: Ouifki, Rachid, Eladdadi, Amina, Stellenbosch University. Faculty of Science. Dept. of Mathematical Sciences. Division Mathematics..

Subjects/Keywords: Immune system – Surveillance; Medical research – Mathematical models; Mathematical models – Differential equations; Cancer – Treatment – Mathematical models; Oncolytic virotherapy; Tumors – Immunological aspects

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mahasa, K. J. (2017). Mathematical Modelling of Tumour-Immune Interactions and Cancer Therapy. (Doctoral Dissertation). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/102597

Chicago Manual of Style (16^th Edition):

Mahasa, Khaphetsi Joseph. “Mathematical Modelling of Tumour-Immune Interactions and Cancer Therapy.” 2017. Doctoral Dissertation, Stellenbosch University. Accessed April 14, 2021. http://hdl.handle.net/10019.1/102597.

MLA Handbook (7^th Edition):

Mahasa, Khaphetsi Joseph. “Mathematical Modelling of Tumour-Immune Interactions and Cancer Therapy.” 2017. Web. 14 Apr 2021.

Vancouver:

Mahasa KJ. Mathematical Modelling of Tumour-Immune Interactions and Cancer Therapy. [Internet] [Doctoral dissertation]. Stellenbosch University; 2017. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10019.1/102597.

Council of Science Editors:

Mahasa KJ. Mathematical Modelling of Tumour-Immune Interactions and Cancer Therapy. [Doctoral Dissertation]. Stellenbosch University; 2017. Available from: http://hdl.handle.net/10019.1/102597

University of Oxford

26. Kueberuwa, Gray L. B. Development of sindbis virus as an oncolytic agent.

Degree: PhD, 2012, University of Oxford

URL: http://ora.ox.ac.uk/objects/uuid:d9737357-ab86-4baf-92a9-b4a21b615fd7 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.580968

► The poor stability of most therapeutic viruses in the human bloodstream is a major obstacle in the field of cancer virotherapy, preventing systemic intravenous delivery… (more)

▼ The poor stability of most therapeutic viruses in the human bloodstream is a major obstacle in the field of cancer virotherapy, preventing systemic intravenous delivery to treat tumour metastases. Delivery is typically limited by inactivation of virus particles by blood components and rapid scavenging by hepatic phagocytes. Members of the Alphavirus family are exposed to blood during natural infections; as such, we hypothesised that evolutionary pressure may have led to blood stability and clearance kinetics superior to those of other viruses currently in development for use as oncolytic agents. Sindbis virus is a member of the Alphavirus family that has shown promising anti-cancer activity in pre-clinical models. A concern for the clinical use of Sindbis virus as an anticancer agent is its pathology in humans, known as Pogosta disease. The symptoms of Pogosta disease may be a result of Sindbis virus replication in neuronal, muscle or haematopoietic tissues. Inhibiting virus replication in these tissues could, therefore, alleviate such potential side effects of virotherapy treatment. Introduction of microRNA response elements, perfectly complementary to microRNAs specifically expressed in liver (miR122), neuronal (miR124), muscle (miR133 and miR206) and haematopoietic (miR142-3p) cells, successfully attenuated SV replication in these tissues. In contrast to all other viruses studied, data presented in this thesis show that Sindbis virus infectivity in vitro is not significantly inhibited by incubation with neat, whole naïve human blood. Despite full infectivity in naïve mouse blood, virus particles were rapidly cleared from the circulation of mice in vivo by the liver. An attempt to decrease the clearance rate by depletion of Kupffer cells through pre-treatment of mice with clodronate liposomes was ineffective. We also explored the use of Sindbis virus packaged in mosquito cells to more closely mimic virus particles exposed to blood in the wild during mosquito mediated transmission, but this also failed to improve virus circulation kinetics in mice. Despite rapid clearance from the circulation, intravenous administration of Sindbis virus had significant anti-cancer efficacy in C57BL/6 mice bearing syngeneic B16F10 metastatic melanomas. Overall, data presented support our proposed use of Sindbis virus as a systemically delivered oncolytic agent and suggest decreasing the rate of clearance by the liver could dramatically enhance therapeutic outcomes. In addition it is shown that microRNA targeting of Sindbis virus provides a means of alleviating potential side effects of the administration of large virus doses.

Subjects/Keywords: 616.9; Oncology; Pharmacology; Viruses; Biology (medical sciences); Tumour pathology; Infectious diseases; Clinical microbiology; Blood; Oncolytic; Virotherapy; MicroRNA; Pharmacokinetics; Virology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kueberuwa, G. L. B. (2012). Development of sindbis virus as an oncolytic agent. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:d9737357-ab86-4baf-92a9-b4a21b615fd7 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.580968

Chicago Manual of Style (16^th Edition):

Kueberuwa, Gray L B. “Development of sindbis virus as an oncolytic agent.” 2012. Doctoral Dissertation, University of Oxford. Accessed April 14, 2021. http://ora.ox.ac.uk/objects/uuid:d9737357-ab86-4baf-92a9-b4a21b615fd7 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.580968.

MLA Handbook (7^th Edition):

Kueberuwa, Gray L B. “Development of sindbis virus as an oncolytic agent.” 2012. Web. 14 Apr 2021.

Vancouver:

Kueberuwa GLB. Development of sindbis virus as an oncolytic agent. [Internet] [Doctoral dissertation]. University of Oxford; 2012. [cited 2021 Apr 14]. Available from: http://ora.ox.ac.uk/objects/uuid:d9737357-ab86-4baf-92a9-b4a21b615fd7 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.580968.

Council of Science Editors:

Kueberuwa GLB. Development of sindbis virus as an oncolytic agent. [Doctoral Dissertation]. University of Oxford; 2012. Available from: http://ora.ox.ac.uk/objects/uuid:d9737357-ab86-4baf-92a9-b4a21b615fd7 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.580968

Virginia Tech

27. Raghunath, Shobana. Targeted Oncolytic Virotherapy Using Newcastle Disease Virus Against Prostate Cancer.

Degree: PhD, Biomedical and Veterinary Sciences, 2012, Virginia Tech

URL: http://hdl.handle.net/10919/77985

► Prostate cancer (CaP) is the second leading cause of cancer related deaths in men in the United States. Currently, androgen depletion is an essential strategy… (more)

▼ Prostate cancer (CaP) is the second leading cause of cancer related deaths in men in the United States. Currently, androgen depletion is an essential strategy for CaP combined with surgery, chemotherapy and radiation. Hormone independent cancer stem cells escaping conventional therapy present a major therapeutic challenge. The available treatment regimens for hormone resistant CaP are only palliative and marginally increase survival. Therefore, novel strategies to eradicate CaP including stem cells are imperative. Oncolytic virus (OV) therapy is a novel approach that overcomes the limitations posed by radiation and chemotherapy. Oncolytic virotherapy of cancer is based on the use of replication competent, tumor selective viruses with limited toxicity. Newcastle Disease Virus (NDV), an avian paramyxovirus, is a safe and promising OV successfully used in many clinical trials. NDV is inherently tumor selective and cytotoxic but replication restricted in normal cells. But, systemically delivered NDV fails to reach solid tumors in therapeutic concentrations and also spreads poorly within the tumors due to barriers including complement, innate immunity and extracellular matrix. Overcoming these hurdles is paramount to realize the exceptional oncolytic efficacy of NDV. Therefore, we engineered the fusion (F) glycoprotein of NDV and generated a recombinant NDV (rNDV) cleavable exclusively by prostate specific antigen (PSA). The rNDV replicated efficiently and specifically only in prostate cancer (CaP) cells but failed to replicate in the absence of PSA. Further, PSA-cleavable rNDV caused specific lysis of androgen independent and dependent/responsive CaP cells with a mean effective concentration (EC50) ranging from 0.01 to 0.1 multiplicity of infection (MOI). PSA retargeted rNDV efficiently lysed three-dimensional prostaspheres, suggesting efficacy in vivo. Also, PSA-cleavable NDV failed to replicate in chicken embryos, indicating absence of pathogenicity to its natural host, chickens. Prostaspheres generated from DU-145 CaP cell line derived xenografts showed self-renewal, proliferative and clonogenic potential in vitro, and exhibited increased tumorigenicity in vivo. Embryonic stem and progenitor cell markers like Nanog, Nestin and CD44 were overexpressed in spheres as compared to the cell line suggesting prostaspheres comprise tumor-initiating cells from CaP. Xenograft and cell line derived prostaspheres were permissive for rNDV replication, when the fusion protein was activated by exogenous PSA. The EC50 against tumor initiating cells was 0.11-0.14 MOI, suggesting an excellent therapeutic margin for in vivo studies. PSA retargeting is likely to enhance the therapeutic index of rNDV owing to tumor restricted replication and enhanced fusogenicity. Our results suggest PSA retargeted rNDV selectively replicates and lyse PSA producing CaP cells including tumor-initiating cells and is a promising candidate for immediate Phase I/II clinical trials. Advisors/Committee Members: Subbiah, Elankumaran (committeechair), Yuan, Lijuan (committee member), Parks, Griffin D. (committee member), Sriranganathan, Nammalwar (committee member), Meng, Xiang-Jin (committee member).

Subjects/Keywords: Tumor initiating cells; Prostate cancer stem cells; Oncolytic virotherapy; Newcastle disease virus; Re targeting; Prostate specific antigen

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Raghunath, S. (2012). Targeted Oncolytic Virotherapy Using Newcastle Disease Virus Against Prostate Cancer. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/77985

Chicago Manual of Style (16^th Edition):

Raghunath, Shobana. “Targeted Oncolytic Virotherapy Using Newcastle Disease Virus Against Prostate Cancer.” 2012. Doctoral Dissertation, Virginia Tech. Accessed April 14, 2021. http://hdl.handle.net/10919/77985.

MLA Handbook (7^th Edition):

Raghunath, Shobana. “Targeted Oncolytic Virotherapy Using Newcastle Disease Virus Against Prostate Cancer.” 2012. Web. 14 Apr 2021.

Vancouver:

Raghunath S. Targeted Oncolytic Virotherapy Using Newcastle Disease Virus Against Prostate Cancer. [Internet] [Doctoral dissertation]. Virginia Tech; 2012. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10919/77985.

Council of Science Editors:

Raghunath S. Targeted Oncolytic Virotherapy Using Newcastle Disease Virus Against Prostate Cancer. [Doctoral Dissertation]. Virginia Tech; 2012. Available from: http://hdl.handle.net/10919/77985

28. Leddon, Jennifer. Oncolytic Herpes Simplex Virus Therapy for the Treatment of Pediatric Rhabdomyosarcoma.

Degree: PhD, Medicine: Immunology, 2015, University of Cincinnati

URL: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427980753

► Multiple studies have indicated that in addition to direct oncolysis, virotherapy promotes an antitumor cytotoxic T cell response important for efficacy. To study this phenomenon… (more)

Subjects/Keywords: Immunology; sarcoma; immunotherapy; oncolytic; virotherapy; HSV

…oncolytic virotherapy—or the use of live naturally non-pathogenic or attenuated viruses to infect… …of oncolytic HSV virotherapy has been demonstrated in a variety of adult and pediatric… …interferon response. The delivery of therapeutic genes by oncolytic virotherapy has tremendous… …tumor responses to oncolytic HSV therapy in immunocompetent and… …recognition. [105, 106]. Oncolytic Herpes Simplex Virus Therapy The concept of using…

12 more images…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Leddon, J. (2015). Oncolytic Herpes Simplex Virus Therapy for the Treatment of Pediatric Rhabdomyosarcoma. (Doctoral Dissertation). University of Cincinnati. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427980753

Chicago Manual of Style (16^th Edition):

Leddon, Jennifer. “Oncolytic Herpes Simplex Virus Therapy for the Treatment of Pediatric Rhabdomyosarcoma.” 2015. Doctoral Dissertation, University of Cincinnati. Accessed April 14, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427980753.

MLA Handbook (7^th Edition):

Leddon, Jennifer. “Oncolytic Herpes Simplex Virus Therapy for the Treatment of Pediatric Rhabdomyosarcoma.” 2015. Web. 14 Apr 2021.

Vancouver:

Leddon J. Oncolytic Herpes Simplex Virus Therapy for the Treatment of Pediatric Rhabdomyosarcoma. [Internet] [Doctoral dissertation]. University of Cincinnati; 2015. [cited 2021 Apr 14]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427980753.

Council of Science Editors:

Leddon J. Oncolytic Herpes Simplex Virus Therapy for the Treatment of Pediatric Rhabdomyosarcoma. [Doctoral Dissertation]. University of Cincinnati; 2015. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427980753

University of Florida

29. Jacobsen, Karly A. A Mathematical Model for Tumor Therapy with a Fusogenic Oncolytic Virus.

Degree: PhD, Mathematics, 2013, University of Florida

URL: https://ufdc.ufl.edu/UFE0045381

► Oncolytic virotherapy is a tumor treatment which uses viruses to selectively target and destroy cancer cells. Clinical trials have demonstrated varying degrees of success for the… (more)

Subjects/Keywords: Budding; Cancer; Mathematical models; Mathematics; Numerical methods; Oncolytic viruses; Ordinary differential equations; Syncytia; Tumors; Uniqueness; advection – boundary – cancer – differential – diffusion – equations – mathematical – model – moving – oncolytic – syncytia – tumor – virotherapy – virus

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jacobsen, K. A. (2013). A Mathematical Model for Tumor Therapy with a Fusogenic Oncolytic Virus. (Doctoral Dissertation). University of Florida. Retrieved from https://ufdc.ufl.edu/UFE0045381

Chicago Manual of Style (16^th Edition):

Jacobsen, Karly A. “A Mathematical Model for Tumor Therapy with a Fusogenic Oncolytic Virus.” 2013. Doctoral Dissertation, University of Florida. Accessed April 14, 2021. https://ufdc.ufl.edu/UFE0045381.

MLA Handbook (7^th Edition):

Jacobsen, Karly A. “A Mathematical Model for Tumor Therapy with a Fusogenic Oncolytic Virus.” 2013. Web. 14 Apr 2021.

Vancouver:

Jacobsen KA. A Mathematical Model for Tumor Therapy with a Fusogenic Oncolytic Virus. [Internet] [Doctoral dissertation]. University of Florida; 2013. [cited 2021 Apr 14]. Available from: https://ufdc.ufl.edu/UFE0045381.

Council of Science Editors:

Jacobsen KA. A Mathematical Model for Tumor Therapy with a Fusogenic Oncolytic Virus. [Doctoral Dissertation]. University of Florida; 2013. Available from: https://ufdc.ufl.edu/UFE0045381

30. Odom, Carl Irwin. Down-modulation of MICA on malignant glioma cells by herpes simplex virus.

Degree: MS, 2012, University of Alabama – Birmingham

URL: http://contentdm.mhsl.uab.edu/u?/etd,1373

►

Glioblastoma Multiforme is a primary malignancy of the central nervous system and is fatal for patients despite surgical resection and radiotherapy. Oncolytic Herpes Simplex Virus… (more)

▼

Glioblastoma Multiforme is a primary malignancy of the central nervous system and is fatal for patients despite surgical resection and radiotherapy. Oncolytic Herpes Simplex Virus (oHSV) vectors deleted of the ?134.5 neurovirulence gene are potential therapies for treating glioblastoma tumors. Although replication in permissive cells is considered the primary mechanism of oHSV mediated tumor clearance, there is evidence that the immune system is part of the tumor clearance mechanism during treatment with oncolytic viruses. Specifically, natural killer (NK) cells may be important for tumor clearance during oHSV therapy. NK cell activation relies partially on the stimulation of activating or inhibitory receptors and their respective ligands encountered on the surfaces of stressed cells. One of the most important and well studied receptor/ligand pairs is the natural killer cell activating receptor Natural Killer Group 2 member D (NKG2D) and the ligand MHC-class-I-polypeptide-related chain A (MICA). Members of the herpes family of viruses have evolved mechanisms of down-modulating MICA surface expression to prevent NK cell activation. This phenomenon is observed with HSV type-1 infection of epithelial tumor lines, yet the mechanism of action is currently unknown. In this work, we tested the hypothesis that HSV infection down-modulates MICA on glioma cells, a phenomenon which could negatively impact the NK cell mediated anti-tumor activity of oHSV. Specificity of MICA down-modulation was studied by analyzing another surface membrane protein, transferrin receptor. The contribution of Virion Host Shut-off (VHS) protein to MICA mRNA degradation as a possible mechanism to surface protein down-modulation was studied by utilization of a VHS deleted virus. These studies demonstrate that MICA is down-modulated from the surface and interior of glioma cells during HSV infection and that down-modulation is specific to MICA compared to levels of transferrin receptor, which in contrast were increased. Comparison of mRNA and protein levels during wild type and VHS deleted recombinant infection suggests that VHS contributes to MICA mRNA degradation but not to protein down-modulation. Continued studies to identify the mechanism of MICA surface down-modulation and will allow for design of oHSV vectors able to optimize anti-tumor immune responses and prolong patient survival.

M.S.

1 online resource (56 p.) :ill., digital, PDF file.

Joint Health Sciences

Glioblastoma Multiforme, Herpes Simplex Virus, Natural Killer cell, MHC-class-I-polypeptide-related chain A (MICA), Virion Host Shut-off, Natural Killer Group 2 member D (NKG2D)

UNRESTRICTED

Advisors/Committee Members: James M. Markert, Additional advisors: Kevin A. Cassady, G. Yancey Gillespie, Peter R. Smith, Mark N. Prichard..

Subjects/Keywords: Down-Regulation<; br>; Glioblastoma – therapy <; br>; Killer Cells, Natural – immunology<; br>; Oncolytic Virotherapy <; br>; Simplexvirus – metabolism

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Odom, C. I. (2012). Down-modulation of MICA on malignant glioma cells by herpes simplex virus. (Masters Thesis). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,1373

Chicago Manual of Style (16^th Edition):

Odom, Carl Irwin. “Down-modulation of MICA on malignant glioma cells by herpes simplex virus.” 2012. Masters Thesis, University of Alabama – Birmingham. Accessed April 14, 2021. http://contentdm.mhsl.uab.edu/u?/etd,1373.

MLA Handbook (7^th Edition):

Odom, Carl Irwin. “Down-modulation of MICA on malignant glioma cells by herpes simplex virus.” 2012. Web. 14 Apr 2021.

Vancouver:

Odom CI. Down-modulation of MICA on malignant glioma cells by herpes simplex virus. [Internet] [Masters thesis]. University of Alabama – Birmingham; 2012. [cited 2021 Apr 14]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1373.

Council of Science Editors:

Odom CI. Down-modulation of MICA on malignant glioma cells by herpes simplex virus. [Masters Thesis]. University of Alabama – Birmingham; 2012. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1373

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