Pre-clinical validation of a pan-cancer CAR-T cell immunotherapy targeting nfP2X7

Chimeric antigen receptor (CAR)-T cell immunotherapy is a novel treatment that genetically modifies the patients’ own T cells to target and kill malignant cells. However, identification of tumour-specific antigens expressed on multiple solid cancer types remains a major challenge. P2X purinoreceptor 7 (P2X7) is a cell surface receptor, and a dysfunctional version of P2X7, named nfP2X7, has been identified on cancer cells from multiple tissues, while being undetectable on healthy cells. We present a prototype human CAR-T construct targeting nfP2X7 showing potential antigen-specific cytotoxicity against twelve solid cancer types (breast, prostate, lung, colorectal, brain and skin). In xenograft mouse models of breast and prostate cancer, CAR-T cells targeting nfP2X7 exhibit robust anti-tumour efficacy. These data indicate that nfP2X7 is a suitable immunotherapy target because of its broad expression on human tumors. CAR-T cells targeting nfP2X7 have potential as a wide-spectrum cancer immunotherapy for solid tumours in humans.

Veronika Bandara, Jade Foeng, Batjargal Gundsambuu, Todd S. Norton, Silvana Napoli, Dylan J. McPeake, Timon S. Tyllis, Elaheh Rohani-Rad, Caitlin Abbott, Stuart J. Mills, Jih L. Tan, Emma J. Thompson, Vasiliki M. Wilet, Victoria J. Nikitakis, Jieren Zheng, Iain Comerford, Adam Johnson, Justin Coombs, Martin K. Oeleh, Carmela Ricciardelli, Allison J. Cowin, Claudine S. Bond, Michael Jensen, Timothy J. Sadlon, Shaun R. McColl, Simon C. Barry