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

Zitation: Dörr, Janina und Gregor, Lisa und Lacher, Sebastian B. und Oner, Arman und Sun, Yi und Piseddu, Ignazio und Fertig, Luisa und Spajic, Sebastijan und Lesch, Stefanie und Michaelides, Stefanos und Seifert, Matthias und Gottschlich, Adrian und Samson, Natasha und Majed, Lina und Briukhovetska, Daria und Simnica, Donjetë und Hartmann, Viktoria und Gabriel, Kathrin und Cohen, Sonia und Boland, Genevieve M. und Andreu-Sanz, David und Carlini, Emanuele und Stock, Sophia und Holtermann, Anne und Müller, Philipp Jie und Strzalkowski, Thaddäus und Trenfy, Marcel P. und Endres, Stefan und Jenkins, Russell W. und Böttcher, Jan P. und 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. Unbekannt

Be­schrei­bung

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.

Stichwörter

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

• Dokumententyp: Daten
• Name der Kontakt­person: Kobold, Sebastian
• E-Mail der Kontaktperson: sebastian.kobold at med.uni-muenchen.de
• Fächer: Medizin
• Dewey Dezimal­klassi­fikation: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie ; 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Eingestellt von: PhD Janina Dörr