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.