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A proton switch for T cell migration and activation

28 months
Approved budget:
Professor Alexander McLellan
Health issue:
Cancer (oncology)
Proposal type:
Explorer Grant
Lay summary
In this proposal, we will exploit the low pH environment of solid tumours to enhance T cell immunotherapy. T cells will be genetically modified with constructs that enhance T cell migration to the low pH environment of tumours and that activate T cells to destroy cancer cells. We will fuse domains of a proton-sensing G-protein coupled receptor (GPCR) to the intracellular signalling domains of a GPCR chemokine-receptor. This will effectively translate suppressive, low pH signalling into migratory and activatory signals for anti-cancer T cells. We propose that chimeric GPCR-modified T cells will be highly effective at infiltrating and destroying solid tumours and represent a novel paradigm for improving immunotherapy for traditionally hard to treat cancers.