학술논문
Pre-clinical validation of a pan-cancer CAR-T cell immunotherapy targeting nfP2X7
Document Type
article
Author
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
Source
Nature Communications, Vol 14, Iss 1, Pp 1-17 (2023)
Subject
Language
English
ISSN
2041-1723
Abstract
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.