Veronika Bandara, Victoria M Niktaras, Vasiliki J Willett, Hayley Chapman, Noor A Lokman, Anne M Macpherson, Silvana Napoli, Batjargal Gundsambuu, Jade Foeng, Timothy J Sadlon, Justin Coombs, Shaun R McColl, Simon C Barry, Martin K Oehler, Carmela Ricciardelli
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In this study, we assessed the cytotoxic effects of nfP2X7-CAR-T cells on ovarian cancer using <i>in vitro</i> and <i>in vivo</i> models.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We evaluated the effects of nfP2X7-CAR-T cells on ovarian cancer cell lines (SKOV-3, OVCAR3, OVCAR5), normal peritoneal cells (LP-9) and primary serous ovarian cancer cells derived from patient ascites <i>in vitro</i> using monolayer and 3D spheroid assays. We also evaluated the effects of nfP2X7-CAR-T cells on patient-derived tissue explants, which recapitulate an intact tumour microenvironment. In addition, we investigated the effect of nfP2X7-CAR-T cells <i>in vivo</i> using the OVCAR-3 xenograft model in NOD-scid IL2Rγnull (NSG) mice.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Our study found that nfP2X7-CAR-T cells were cytotoxic and significantly inhibited survival of OVCAR3, OVCAR5 and primary serous ovarian cancer cells compared with un-transduced CD3<sup>+</sup> T cells <i>in vitro</i>. However, no significant effects of nfP2X7-CAR-T cells were observed for SKOV3 or normal peritoneal cells (LP-9) cells with low P2X7 receptor expression. Treatment with nfP2X7-CAR-T cells increased apoptosis compared with un-transduced T cells in patient-derived explants and correlated with CD3 positivity. Treatment with nfP2X7-CAR-T cells significantly reduced OVCAR3 tumour burden in mice compared with un-transduced CD3 cells for 7–8 weeks.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>This study demonstrates that nfP2X7-CAR-T cells have great potential to be developed as a novel immunotherapy for ovarian cancer.</p>\n </section>\n </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 5","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1512","citationCount":"0","resultStr":"{\"title\":\"Engineered CAR-T cells targeting the non-functional P2X purinoceptor 7 (P2X7) receptor as a novel treatment for ovarian cancer\",\"authors\":\"Veronika Bandara, Victoria M Niktaras, Vasiliki J Willett, Hayley Chapman, Noor A Lokman, Anne M Macpherson, Silvana Napoli, Batjargal Gundsambuu, Jade Foeng, Timothy J Sadlon, Justin Coombs, Shaun R McColl, Simon C Barry, Martin K Oehler, Carmela Ricciardelli\",\"doi\":\"10.1002/cti2.1512\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objectives</h3>\\n \\n <p>Recent studies have identified expression of the non-functional P2X7 (nfP2X7) receptor on various malignant cells including ovarian cancer, but not on normal cells, which makes it a promising tumour-associated antigen candidate for chimeric antigen receptor (CAR)-T-cell immunotherapies. 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Engineered CAR-T cells targeting the non-functional P2X purinoceptor 7 (P2X7) receptor as a novel treatment for ovarian cancer
Objectives
Recent studies have identified expression of the non-functional P2X7 (nfP2X7) receptor on various malignant cells including ovarian cancer, but not on normal cells, which makes it a promising tumour-associated antigen candidate for chimeric antigen receptor (CAR)-T-cell immunotherapies. In this study, we assessed the cytotoxic effects of nfP2X7-CAR-T cells on ovarian cancer using in vitro and in vivo models.
Methods
We evaluated the effects of nfP2X7-CAR-T cells on ovarian cancer cell lines (SKOV-3, OVCAR3, OVCAR5), normal peritoneal cells (LP-9) and primary serous ovarian cancer cells derived from patient ascites in vitro using monolayer and 3D spheroid assays. We also evaluated the effects of nfP2X7-CAR-T cells on patient-derived tissue explants, which recapitulate an intact tumour microenvironment. In addition, we investigated the effect of nfP2X7-CAR-T cells in vivo using the OVCAR-3 xenograft model in NOD-scid IL2Rγnull (NSG) mice.
Results
Our study found that nfP2X7-CAR-T cells were cytotoxic and significantly inhibited survival of OVCAR3, OVCAR5 and primary serous ovarian cancer cells compared with un-transduced CD3+ T cells in vitro. However, no significant effects of nfP2X7-CAR-T cells were observed for SKOV3 or normal peritoneal cells (LP-9) cells with low P2X7 receptor expression. Treatment with nfP2X7-CAR-T cells increased apoptosis compared with un-transduced T cells in patient-derived explants and correlated with CD3 positivity. Treatment with nfP2X7-CAR-T cells significantly reduced OVCAR3 tumour burden in mice compared with un-transduced CD3 cells for 7–8 weeks.
Conclusion
This study demonstrates that nfP2X7-CAR-T cells have great potential to be developed as a novel immunotherapy for ovarian cancer.
期刊介绍：
Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.
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