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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.

SUBMITTER: Bandara V

PROVIDER: S-EPMC10491676 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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

Bandara Veronika V Foeng Jade J Gundsambuu Batjargal B Norton Todd S TS Napoli Silvana S McPeake Dylan J DJ Tyllis Timona S TS Rohani-Rad Elaheh E Abbott Caitlin C Mills Stuart J SJ Tan Lih Y LY Thompson Emma J EJ Willet Vasiliki M VM Nikitaras Victoria J VJ Zheng Jieren J Comerford Iain I Johnson Adam A Coombs Justin J Oehler Martin K MK Ricciardelli Carmela C Cowin Allison J AJ Bonder Claudine S CS Jensen Michael M Sadlon Timothy J TJ McColl Shaun R SR Barry Simon C SC

Nature communications 20230908 1

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 ...[more]

PMID: 37684239

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Dataset Information

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

Publications

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

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