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You searched for subject:(TLR ligands). Showing records 1 – 2 of 2 total matches.

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Leiden University

1. Varypataki, E.M. Liposome-based synthetic long peptide vaccines for cancer immunotherapy.

Degree: 2016, Leiden University

Synthetic long peptides (SLP) derived from cancer-associated antigens hold great promise as well-defined antigens for cancer immunotherapy. Clinical studies showed that SLP vaccines have functional potency when applied to pre-malignant stage patients, but need to be improved for use as a therapeutic intervention against tumours. So far, SLPs have been administered in Montanide ISA-51, a water-in-oil formulation with reported important drawbacks and induced local side effects. Therefore, there is an urgent need for replacement of Montanide by more potent and safe alternatives. In this thesis, the concept of cationic liposome-based formulations was introduced, as the backbone for improved delivery of SLPs for cancer therapeutic vaccination. The developed formulation’s ability to induce efficient immune responses able to control tumour outgrowth in aggressive independent tumour models, makes cationic liposomes a very promising platform for SLP-based cancer immunotherapy. Their flexibility regarding the properties of loaded SLPs, their relative inexpensive production and the possibility to administer them via different delivery routes are all in favour for liposomal SLP-based cancer immunotherapy to become reality soon. Advisors/Committee Members: Supervisors: Wim Jiskoot, Ferry Ossendorp.

Subjects/Keywords: Vaccine-delivery; Cationic liposomes; Nanoparticles; TLR-ligands; Cellular immunity; HPV-E7; Tumour models; Vaccine-delivery; Cationic liposomes; Nanoparticles; TLR-ligands; Cellular immunity; HPV-E7; Tumour models

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

APA (6th Edition):

Varypataki, E. M. (2016). Liposome-based synthetic long peptide vaccines for cancer immunotherapy. (Doctoral Dissertation). Leiden University. Retrieved from http://hdl.handle.net/1887/39775

Chicago Manual of Style (16th Edition):

Varypataki, E M. “Liposome-based synthetic long peptide vaccines for cancer immunotherapy.” 2016. Doctoral Dissertation, Leiden University. Accessed January 16, 2021. http://hdl.handle.net/1887/39775.

MLA Handbook (7th Edition):

Varypataki, E M. “Liposome-based synthetic long peptide vaccines for cancer immunotherapy.” 2016. Web. 16 Jan 2021.

Vancouver:

Varypataki EM. Liposome-based synthetic long peptide vaccines for cancer immunotherapy. [Internet] [Doctoral dissertation]. Leiden University; 2016. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1887/39775.

Council of Science Editors:

Varypataki EM. Liposome-based synthetic long peptide vaccines for cancer immunotherapy. [Doctoral Dissertation]. Leiden University; 2016. Available from: http://hdl.handle.net/1887/39775

2. Heffernan, Michael John. Biodegradable polymeric delivery systems for protein subunit vaccines.

Degree: PhD, Biomedical Engineering, 2008, Georgia Tech

The prevention and treatment of cancer and infectious diseases requires vaccines that can mediate cytotoxic T lymphocyte-based immunity. A promising strategy is protein subunit vaccines composed of purified protein antigens and immunostimulatory adjuvants, such as Toll-like receptor (TLR) agonists. In this research, we developed two new biodegradable polymeric delivery vehicles for protein antigens and TLR agonists, as model vaccine delivery systems. This work was guided by the central hypothesis that an effective vaccine delivery system would have stimulus-responsive degradation and release, biodegradability into excretable non-acidic degradation products, and the ability to incorporate various TLR-inducing adjuvants. The first vaccine delivery system is a cross-linked polyion complex micelle which efficiently encapsulates proteins, DNA, and RNA. The micelle-based delivery system consists of a block copolymer of poly(ethylene glycol) (PEG) and poly(L-lysine), cross-linked by dithiopyridyl side groups to provide transport stability and intracellular release. The second delivery system consists of solid biodegradable microparticles encapsulating proteins, nucleic acids, and hydrophobic compounds. The microparticles are composed of pH-sensitive polyketals, which are a new family of hydrophobic, linear polymers containing backbone ketal linkages. Polyketals are synthesized via a new polymerization method based on the acetal exchange reaction and degrade into non-acidic, excretable degradation products. In addition, the technique of hydrophobic ion pairing was utilized to enhance the encapsulation of ovalbumin, DNA, and RNA in polyketal microparticles via a single emulsion method. Using in vitro and in vivo immunological models, we demonstrated that the micelle- and polyketal-based vaccine delivery systems enhanced the cross-priming of cytotoxic T lymphocytes. The model vaccines were composed of ovalbumin antigen and various TLR-inducing adjuvants including CpG-DNA, monophosphoryl lipid A, and dsRNA. The results demonstrate that the cross-linked micelles and polyketal microparticles have considerable potential as delivery systems for protein-based vaccines. Advisors/Committee Members: Dr. Niren Murthy (Committee Chair), Dr. Carson Meredith (Committee Member), Dr. Julia Babensee (Committee Member), Dr. Mark Prausnitz (Committee Member), Dr. Ravi Bellamkonda (Committee Member).

Subjects/Keywords: Vaccine delivery; Drug delivery; Microencapsulation; Nanospheres; Microspheres; Nanoparticles; Polyacetal; PH-responsive; TLR ligands; Poly(I)-poly(C); Acid-degradable; Vaccines; Polymeric drug delivery systems; Biodegradable plastics

…containing adaptor inducing IFN-β TLR Toll-like receptor TNF-α Tumor necrosis factor alpha xiv… …Delivery of protein antigens and TLR agonists to APCs elicits cellular immunity through the… …for protein/TLR vaccines, there is a need for further improvement with regard to the carrier… …was to develop improved delivery vehicles for protein/TLR-based vaccines, guided by the… …ability to incorporate various TLR-inducing adjuvants. The first two specific aims were centered… 

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

APA (6th Edition):

Heffernan, M. J. (2008). Biodegradable polymeric delivery systems for protein subunit vaccines. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/24787

Chicago Manual of Style (16th Edition):

Heffernan, Michael John. “Biodegradable polymeric delivery systems for protein subunit vaccines.” 2008. Doctoral Dissertation, Georgia Tech. Accessed January 16, 2021. http://hdl.handle.net/1853/24787.

MLA Handbook (7th Edition):

Heffernan, Michael John. “Biodegradable polymeric delivery systems for protein subunit vaccines.” 2008. Web. 16 Jan 2021.

Vancouver:

Heffernan MJ. Biodegradable polymeric delivery systems for protein subunit vaccines. [Internet] [Doctoral dissertation]. Georgia Tech; 2008. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1853/24787.

Council of Science Editors:

Heffernan MJ. Biodegradable polymeric delivery systems for protein subunit vaccines. [Doctoral Dissertation]. Georgia Tech; 2008. Available from: http://hdl.handle.net/1853/24787

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