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In this study, we identified a consistently expressed target antigen, podoplanin (PDPN), and evaluated the potential of a PDPN-CAR T cell and GD2-CAR T cell blend to target heterogeneous GBM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Target antigen screening included clinical samples, cell lines and healthy tissues, as well as public RNA sequencing datasets. The anti-tumor function of CAR T cells was examined in co-culture experiments with GBM cell lines and patient-derived organoids (PDOs), and in vivo after locoregional delivery in orthotopic xenograft models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CAR T cells demonstrated strong anti-tumor activity against several cell lines and PDOs from multiple patients. PDPN and GD2 were expressed in all PDOs, and regardless of the antigen expression pattern, the CAR T cell blend induced significantly higher apoptosis levels in organoids compared with single-antigen targeting CAR T cells. In vivo, we observed efficient tumor regression after locoregional administration of monospecific CAR T cells. While heterogeneous orthotopic tumors eventually relapsed in these groups, therapy with the CAR T cell blend significantly increased overall survival and even achieved a cure in the majority of mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This novel PDPN\/GD2 CAR T cell blend demonstrated robust efficacy in advanced preclinical GBM models, suggesting its potential to treat heterogeneous GBM and address limitations associated with single-antigen CAR T cell therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-014693","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:15:10Z","timestamp":1780503310000},"page":"e014693","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Novel CAR T cell blend targeting PDPN and GD2 to overcome glioblastoma 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