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http://hdl.handle.net/11375/26940
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DC Field | Value | Language |
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dc.contributor.advisor | Bramson, Jonathan | - |
dc.contributor.author | Asbury, Sarah | - |
dc.date.accessioned | 2021-09-30T15:30:52Z | - |
dc.date.available | 2021-09-30T15:30:52Z | - |
dc.date.issued | 2021 | - |
dc.identifier.uri | http://hdl.handle.net/11375/26940 | - |
dc.description.abstract | Engineered T cell therapies have had unprecedented success in treating hematological malignancies. However, their use is limited by expensive treatment costs – priced at approximately $500,000 CAD for a single-dose of CAR-T cell therapy. γδ T cells are a candidate for allogeneic engineered T cell therapies, which can be mass manufactured to reduce the cost of goods. In this thesis we investigate γδ T cells engineered with a T cell Antigen Coupler targeting BCMA (BCMA-TAC) for the treatment of Multiple Myeloma – an incurable hematological malignancy. We optimized a manufacturing method to transduce γδ T cells with a GaLV-pseudotyped γ-retrovirus encoding BCMA-TAC and demonstrated that BCMA-TAC γδ T cells rapidly and specifically kill Multiple Myeloma tumour cells. We also investigated the potential for a combination therapy using engineered γδ T cells and monoclonal antibodies. Such a combination therapy may be synergistic, because γδ T cells express CD16 and can respond to antibody opsonized cells via direct cytotoxicity or phagocytosis. While degranulation of BCMA-TAC γδ T cells was enhanced by CD16 stimulation, we did not observe any improvements in direct cytotoxicity against antibody-opsonized tumour cells. Overall, our results demonstrate that BCMA-TAC γδ T cells can directly target and kill Multiple Myeloma tumour cells, but whether monoclonal antibodies can be used to further enhance their anti-tumour properties remains unclear. | en_US |
dc.language.iso | en | en_US |
dc.title | TAC Engineered γδ T cells for Multiple Myeloma | 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 Science (MSc) | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Asbury_Sarah_E_2021Sep_MSc.pdf | 9.73 MB | Adobe PDF | View/Open |
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