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

Abstract

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 purinoceptor 7 (P2X7) is a cell surface expressed ATP gated cation channel, 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 tumours. CAR-T cells targeting nfP2X7 have potential as a wide-spectrum cancer immunotherapy for solid tumours in humans.

• Authors: Veronika Bandara, Jade Foeng, Batjargal Gundsambuu, Todd S Norton, Silvana Napoli, Dylan J McPeake, Timona S Tyllis, Elaheh Rohani-Rad, Caitlin Abbott, Stuart J Mills, Lih Y Tan, Emma J Thompson, Vasiliki M Willet, Victoria J Nikitaras, Jieren Zheng, Iain Comerford, Adam Johnson, Justin Coombs, Martin K Oehler, Carmela Ricciardelli, Allison J Cowin, Claudine S Bonder, Michael Jensen, Timothy J Sadlon, Shaun R McColl, Simon C Barry
• Journal: Nature communications (Nat Commun) Vol. 14 Issue 1 Pg. 5546 (09 08 2023) ISSN: 2041-1723 [Electronic] England
• PMID: 37684239 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. Springer Nature Limited.

Topics

• Male
• Humans
• Animals
• Mice
• Prostatic Neoplasms
• Immunotherapy
• Brain
• Breast
• Cell Membrane
• Disease Models, Animal