Source data: Ablation of prostaglandin E2-signaling through dual receptor knock-out in CAR T cells enhances therapeutic efficacy in solid tumors

Citation: Dörr, Janina and Gregor, Lisa and Lacher, Sebastian B. and Oner, Arman and Sun, Yi and Piseddu, Ignazio and Fertig, Luisa and Spajic, Sebastijan and Lesch, Stefanie and Michaelides, Stefanos and Seifert, Matthias and Gottschlich, Adrian and Samson, Natasha and Majed, Lina and Briukhovetska, Daria and Simnica, Donjetë and Hartmann, Viktoria and Gabriel, Kathrin and Cohen, Sonia and Boland, Genevieve M. and Andreu-Sanz, David and Carlini, Emanuele and Stock, Sophia and Holtermann, Anne and Müller, Philipp Jie and Strzalkowski, Thaddäus and Trenfy, Marcel P. and Endres, Stefan and Jenkins, Russell W. and Böttcher, Jan P. and Kobold, Sebastian: Source data: Ablation of prostaglandin E2-signaling through dual receptor knock-out in CAR T cells enhances therapeutic efficacy in solid tumors. 6. November 2025. Open Data LMU. 10.5282/ubm/data.713

Abstract

This entry contains the datasets associated with the publication "Ablation of prostaglandin E2-signaling through dual receptor knock-out in CAR T cells enhances therapeutic efficacy in solid tumors". Abstract: The efficacy of chimeric antigen receptor (CAR) T cell therapy in solid cancers is limited by immunosuppression in the tumor microenvironment (TME). Prostaglandin E2 (PGE2) is a key factor locally inhibiting T cell function. We hypothesized that targeted ablation of PGE2 signaling in CAR T cells may enhance their activity in PGE2-rich solid tumors. Here, we generated knockout CAR T cells double deficient for the PGE2-receptors EP2 and EP4 (EP2-/-EP4-/-) by CRISPR-Cas9 engineering. EP2-/-EP4-/- CAR T cells expanded unabatedly in the presence of PGE2. Further, they effectively controlled syngeneic and human xenograft tumor models in vivo, which was accompanied by intratumoral accumulation and persistence of modified T cells. Improved anti-tumor activity was also observed against patient-derived tumor samples from pancreatic ductal adenocarcinoma (PDAC), colorectal (CRC) and neuroendocrine (NET) cancer patients. Our data uncovers the detrimental impact of PGE2-mediated suppression on CAR T cell efficacy and highlights EP2 and EP4 targeting as potential strategy.

Uncontrolled Keywords

CAR T cell therapy, Prostaglandin E2, solid tumor therapy, overcoming tumor immunosuppression

• Item Type: Data
• Contact Person: Kobold, Sebastian
• E-Mail of Contact: sebastian.kobold at med.uni-muenchen.de
• Subjects: Medicine
• Dewey Decimal Classification: 500 Natural sciences and mathematics; 500 Natural sciences and mathematics > 570 Life sciences; 600 Technology, Medicine; 600 Technology, Medicine > 610 Medical sciences and medicine