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Overcoming the limitations of adoptive T-cell therapy by genetic modification

36 months
Approved budget:
Professor Antony Braithwaite
Dr Kunyu Li
Professor Sarah Young
Professor Merilyn Hibma
Dr Kevin Ly
Health issue:
Cancer (oncology)
Proposal type:
Explorer Grant
Lay summary
Despites its success in treating haematological cancer, ACT using chimeric antigen receptor-expressing (CAR) T cells is much less successful in solid cancers. This is due to the lack of tumour specific antigens and also other hurdles that limit T cell responses in solid tumours. Here, we wish to explore a new form of genetic modification of T cells to overcome the limitation of cell survival and functional capacity in ACT. We will transduce a p53 variant, Δ133p53, which has been found to provide growth and survival advantage in tumour cells, into T cells using lentiviral particles. We will than test survival, expansion, and anti-tumour function of these Δ133p53 expressing T cells in an animal model of melanoma. The findings of this study could potentially change our views on the Δ133p53 gene, and also provide a new therapeutic oppornity to enhance the potential of our immune cells to treat diseases.