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

713 58 4338 4 17176 document 4338 Fig1, ED1.zip application/zip 28a6620c5bd6793822eece924e24f799 MD5 3114617555 2025-11-04 13:46:46 https://data.ub.uni-muenchen.de/713/1/Fig1%2C%20ED1.zip 713 1 3 application/zip other .zip containing all data related to Figure 1 and Extended Data Figure 1 de public

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4345 8 17220 document 4345 README.txt text/plain 55648845c0b5cdb7456a2654a263b792 MD5 795 2025-11-10 07:29:07 https://data.ub.uni-muenchen.de/713/8/README.txt 713 8 2 text/plain text/plain README de public

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http://eprints.org/relation/isVersionOf https://data.ub.uni-muenchen.de/id/document/4345 http://eprints.org/relation/isVolatileVersionOf https://data.ub.uni-muenchen.de/id/document/4345 http://eprints.org/relation/isIndexCodesVersionOf https://data.ub.uni-muenchen.de/id/document/4345 archive 1187 disk0/00/00/07/13 2025-11-10 07:34:27 2025-11-14 08:36:12 2025-11-14 08:36:05 data show 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. eng Dörr Janina Gregor Lisa Lacher Sebastian B. Oner Arman Sun Yi Piseddu Ignazio Fertig Luisa Spajic Sebastijan Lesch Stefanie Michaelides Stefanos Seifert Matthias Gottschlich Adrian Samson Natasha Majed Lina Briukhovetska Daria Simnica Donjetë Hartmann Viktoria Gabriel Kathrin Cohen Sonia Boland Genevieve M. Andreu-Sanz David Carlini Emanuele Stock Sophia Holtermann Anne Müller Philipp Jie Strzalkowski Thaddäus Trenfy Marcel P. Endres Stefan Jenkins Russell W. Böttcher Jan P. Kobold Sebastian 2025-11-06 500 570 600 610 10.5282/ubm/data.713 https://doi.org/10.5282/ubm/data.713 public CAR T cell therapy Prostaglandin E2 solid tumor therapy overcoming tumor immunosuppression en cc-by Kobold Sebastian fak07 Source data: Ablation of prostaglandin E2-signaling through dual receptor knock-out in CAR T cells enhances therapeutic efficacy in solid tumors