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http://hdl.handle.net/11375/30109
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DC Field | Value | Language |
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dc.contributor.advisor | Bramson, Jonathan | - |
dc.contributor.author | Morris, Claire | - |
dc.date.accessioned | 2024-08-28T15:20:24Z | - |
dc.date.available | 2024-08-28T15:20:24Z | - |
dc.date.issued | 2024 | - |
dc.identifier.uri | http://hdl.handle.net/11375/30109 | - |
dc.description.abstract | Creating a universal-prime boost strategy using multi-specific T cells from the tumour infiltrating lymphocytes (TIL) population can enhance the success of adoptive T cell therapies (ACT). ACT, as a personalized living-drug, is often a last resort due to its extensive time, cost, and labor requirements, making it largely inaccessible. Vaccines encoding personalized tumour-associated antigens (TAA) have proven to be potent boosters for ACT. This combination has shown success in (1) promoting T cell proliferation in vivo and (2) inducing immune infiltration into the solid tumour microenvironment. TIL offer a plethora of TAA-specific T-cell receptors (TCRs) when successfully isolated and expanded. Synthetic receptors can be engineered into TIL to recognize any specified antigen, including those matched in vaccines. Previously, we validated combining ACT with an oncolytic virus vaccine (OVV) “boost” through a synthetic receptor to promote in vivo expansion of naïve splenocytes in a proof-of- concept TCR-transgenic synergetic murine model. Here, we report on the feasibility of isolating and engineering polyclonal, tumour-specific T cells from TIL and tumour- draining lymph nodes, evaluating them functionally. We further investigate the matched CAR/OVV system in another distinct TCR transgenic model and return to the first proof- of-concept model to uncover the biological mechanisms of our combination therapy to improve anti-tumour efficacy. Uniting a universal OV vaccine with a matched universal CAR creates an “off-the-shelf” combination, allowing any T cell product to be engineered. This approach reduces the resource burden of traditional ACT, making it more accessible to all cancer types. | en_US |
dc.language.iso | en | en_US |
dc.subject | Cancer | en_US |
dc.subject | Immunology | en_US |
dc.title | Developing an engineered T cell product for universal vaccination-based boosting in adoptive cell therapies | en_US |
dc.title.alternative | Oncolytic virus vaccination to expand engineered T cells | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Biochemistry and Biomedical Sciences | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Health Sciences (MSc) | en_US |
dc.description.layabstract | Adoptive T cell therapy (ACT) uses a patient's immune cells to fight cancer but is often a last resort due to high costs and labor. Our research aims to make ACT more accessible by combining it with therapeutic cancer vaccines that can contain any protein, including cancer proteins, and boost ACT’s effectiveness. We engineered T cells with synthetic receptors to recognize the vaccine’s protein and developed a universal system pairing these T cells with a specially designed oncolytic virus vaccine (OVV). This combination promotes T cell expansion and improves immune response against tumours. We tested this system in multiple models, demonstrating enhanced T cell function and tumour targeting in one model, but challenges in another. Investigating the mechanisms, we sought to identify ways to improve the therapy’s efficacy. Our "off-the- shelf" solution reduces costs and resources, making this powerful cancer treatment more accessible to a wider range of patients. | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Morris_Claire_G_FinalSubmissionAugust2024_MSc.pdf | 12.63 MB | Adobe PDF | View/Open |
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