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http://hdl.handle.net/11375/26940
Title: | TAC Engineered γδ T cells for Multiple Myeloma |
Authors: | Asbury, Sarah |
Advisor: | Bramson, Jonathan |
Department: | Biochemistry and Biomedical Sciences |
Publication Date: | 2021 |
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. |
URI: | http://hdl.handle.net/11375/26940 |
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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