biostudies-literatureWehrli MDKMS FoundationNIAID NIH HHSSociedad Española de Oncología MédicaNational Institutes of HealthSwiss National Science FoundationDeutsche ForschungsgemeinschaftNational Cancer InstituteNCI NIH HHSHopper-Belmont FoundationAmerican-Italian Cancer FoundationNIGMS NIH HHSCRIS Cancer FoundationItalian Foundation for Cancer Research1859-1877https://www.ebi.ac.uk/biostudies/studies/S-EPMC11062832biostudies-literatureUnknown30(9)<h4>Purpose</h4>Targeting solid tumors with chimeric antigen receptor (CAR) T cells remains challenging due to heterogenous target antigen expression, antigen escape, and the immunosuppressive tumor microenvironment (TME). Pancreatic cancer is characterized by a thick stroma generated by cancer-associated fibroblasts (CAF), which may contribute to the limited efficacy of mesothelin-directed CAR T cells in early-phase clinical trials. To provide a more favorable TME for CAR T cells to target pancreatic ductal adenocarcinoma (PDAC), we generated T cells with an antimesothelin CAR and a secreted T-cell-engaging molecule (TEAM) that targets CAF through fibroblast activation protein (FAP) and engages T cells through CD3 (termed mesoFAP CAR-TEAM cells).<h4>Experimental design</h4>Using a suite oClinical cancer research : an official journal of the American Association for Cancer ResearchMesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma.PMC11062832T32 AI007529outback2021_6DKMS-SLS-JHRG-2020-04186739466535590T32 AI007247K08CA226391P400PM_186739U01 CA228963R01 CA238268U01CA228963R01 CA235412R01CA2354122T32AI007247-39R01CA238268K08 CA248710T32 GM144273K08CA248710K08 CA226391Boland GMBirocchi FLarson RCKorell FXu KHZhang RJaffee EMKuo AGrauwet KScarfo ITing DTZheng LSchmidts AMaus MVAnekal PVSong YLeick MBMontero Llopis PJan MChoi BDJenkins RWNieman LTSun YWehrli MBurkhart RABerger TRKienka TGuinn SSilva HArmstrong TDBouffard AAAlmazan AJSalas-Benito DFu JKann MCLiss ASZhu QBailey SRZimmerman JWfalseMesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma.<h4>Purpose</h4>Targeting solid tumors with chimeric antigen receptor (CAR) T cells remains challenging due to heterogenous target antigen expression, antigen escape, and the immunosuppressive tumor microenvironment (TME). Pancreatic cancer is characterized by a thick stroma generated by cancer-associated fibroblasts (CAF), which may contribute to the limited efficacy of mesothelin-directed CAR T cells in early-phase clinical trials. To provide a more favorable TME for CAR T cells to target pancreatic ductal adenocarcinoma (PDAC), we generated T cells with an antimesothelin CAR and a secreted T-cell-engaging molecule (TEAM) that targets CAF through fibroblast activation protein (FAP) and engages T cells through CD3 (termed mesoFAP CAR-TEAM cells).<h4>Experimental design</h4>Using a suite o2024-01-01T00:00:00Z2024 May2026-06-02T22:13:14.389Z2025-04-06T14:25:50.919ZS-EPMC110628323839368210.1158/1078-0432.CCR-23-384110.1158/1078-0432.ccr-23-3841