{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:11:23Z","timestamp":1784956283596,"version":"3.55.0"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T00:00:00Z","timestamp":1716422400000},"content-version":"vor","delay-in-days":143,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Recent studies have identified expression of the non\u2010functional P2X7 (nfP2X7) receptor on various malignant cells including ovarian cancer, but not on normal cells, which makes it a promising tumour\u2010associated antigen candidate for chimeric antigen receptor (CAR)\u2010T\u2010cell immunotherapies. In this study, we assessed the cytotoxic effects of nfP2X7\u2010CAR\u2010T cells on ovarian cancer using <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated the effects of nfP2X7\u2010CAR\u2010T cells on ovarian cancer cell lines (SKOV\u20103, OVCAR3, OVCAR5), normal peritoneal cells (LP\u20109) and primary serous ovarian cancer cells derived from patient ascites <jats:italic>in\u00a0vitro<\/jats:italic> using monolayer and 3D spheroid assays. We also evaluated the effects of nfP2X7\u2010CAR\u2010T cells on patient\u2010derived tissue explants, which recapitulate an intact tumour microenvironment. In addition, we investigated the effect of nfP2X7\u2010CAR\u2010T cells <jats:italic>in vivo<\/jats:italic> using the OVCAR\u20103 xenograft model in NOD\u2010scid IL2R\u03b3null (NSG) mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our study found that nfP2X7\u2010CAR\u2010T cells were cytotoxic and significantly inhibited survival of OVCAR3, OVCAR5 and primary serous ovarian cancer cells compared with un\u2010transduced CD3<jats:sup>+<\/jats:sup> T\u00a0cells <jats:italic>in vitro<\/jats:italic>. However, no significant effects of nfP2X7\u2010CAR\u2010T cells were observed for SKOV3 or normal peritoneal cells (LP\u20109) cells with low P2X7 receptor expression. Treatment with nfP2X7\u2010CAR\u2010T cells increased apoptosis compared with un\u2010transduced T\u00a0cells in patient\u2010derived explants and correlated with CD3 positivity.\u00a0Treatment with nfP2X7\u2010CAR\u2010T cells significantly reduced OVCAR3 tumour burden in mice compared with un\u2010transduced CD3 cells for 7\u20138\u2009weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrates that nfP2X7\u2010CAR\u2010T cells have great potential to be developed as a novel immunotherapy for ovarian cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1512","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T04:42:53Z","timestamp":1716525773000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Engineered CAR\u2010T\u00a0cells targeting the non\u2010functional P2X purinoceptor 7 (P2X7) receptor as a novel treatment for ovarian 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