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Manipulating T lymphocyte homing and activation for cancer immunotherapy.

Ann Ager

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Funding source

Wellcome Trust (WT)
Our experiments are directed at enhancing the potency of adoptive T cell immunotherapy (ACT). To date, all three applicants have made a series of independent observations on different aspects of T cell biology following genetic manipulation of mouse T cells. Each of these genetic changes has had the effect of significantly promoting anti-tumour immune responses. A natural progression of these findings, to be pursued in this grant, is to explore in the context of adoptive T cell immunotherapy, the potential overlapping, additive or synergistic effects of combining these genetic manipulations of T cells. Specifically, in this proposal we will: Determine whether adoptive transfer of CD8 T cells with maintained L-selectin and/or deficiency in SHP-1 induces regression of vascularised tumours in mouse Determine whether the removal of Tregs from the tumour bearing hosts has an additional or synergistic effect on CD8 mediated tumour regression in mice Determine whether human CD8+ T cell reactivity to tumour antigens can be similarly modified by maintained L-selectin and/or SHP-1 deficiency and whether sensitivity to Tregs is altered

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