Main content

Enhancing Cancer Immunotherapies Using Cell-Based or Viral Vectored Vaccines

Show simple item record

dc.contributor.advisor Bridle, Byram
dc.contributor.author Mould, Robert
dc.date.accessioned 2020-06-05T14:10:16Z
dc.date.copyright 2020-06
dc.date.created 2020-05-27
dc.date.issued 2020-06-05
dc.identifier.uri http://hdl.handle.net/10214/18033
dc.description.abstract Over the past decade there has been a dramatic increase of interest in cancer immunotherapy due to a variety of advantages over conventional methods and promising results. Cancer immunotherapy is a collection of treatment modalities used to treat cancer by taking advantage of the potency and specificity of the immune system. While immunotherapy, as a whole, can encompass many facets of the immune system, a primary focus is the generation or enhancement of a tumour-specific immune response. Herein, we describe several methods that enhance tumor-specific immunity by exploiting the potent immunogenicity of viral vectored, or dendritic cell (DC)-based vaccines. Viral vectors are a useful vaccine vehicle due to their innate ability to provide an antigen source in the form of a recombinant transgene, while in an immunogenic context. The generation of anti-tumor immunity in this context relies on endogenous antigen-presenting cells, of which DCs are the most potent. DCs have a superior capacity to engage naïve T cells to facilitate a clonal expansion of a tumour-specific repertoire. As such DCs are thought to be an ideal candidate for a cell-based cancer vaccine. Unfortunately, both viral vector and DC-based vaccines have many obstacles that need to be carefully avoided in order to generate efficacious results. To this end we have described several methods of overcoming some of these obstacles that have led to enhanced therapeutic benefits. Firstly, we described how multi-site injections, where a vaccine dose is spread between two or more limbs, can enhance the magnitude of a global vaccine response when compared to a single bolus. We also characterized a novel method of epitope mapping that can uncover epitopes for even poorly immunogenic proteins using a heterologous virus-based prime-boost strategy. Finally, we performed an in-depth analysis of the various subsets contained within murine bone marrow-derived DC cultures. We demonstrated that true DCs make up a minority of a heterogenous population of cells and are exclusively responsible for generating T cell immunity. Taken together our results demonstrated several means of enhancing cancer immunotherapies. en_US
dc.language.iso en en_US
dc.rights Attribution-NonCommercial-NoDerivatives 4.0 International *
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/ *
dc.subject Immunology en_US
dc.subject Cancer en_US
dc.subject Vaccines en_US
dc.subject Virology en_US
dc.subject Dendritic Cells en_US
dc.subject Epitope en_US
dc.title Enhancing Cancer Immunotherapies Using Cell-Based or Viral Vectored Vaccines en_US
dc.type Thesis en_US
dc.degree.programme Pathobiology en_US
dc.degree.name Doctor of Philosophy en_US
dc.degree.department Department of Pathobiology en_US
dc.description.embargo 2021-05-27
dc.rights.license All items in the Atrium are protected by copyright with all rights reserved unless otherwise indicated.


Files in this item

Files Size Format View Description
Mould_Robert_202006_PhD.pdfuntranslated 4.759Mb PDF View/Open Robert Mould's PhD Thesis

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivatives 4.0 International Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International