 Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinomaDaniel Schäfer,
Stefan Tomiuk,
Laura N. Küster,
Wa’el Al Rawashdeh,
Janina Henze,
German Tischler-Höhle,
David J. Agorku,
Janina Brauner,
Cathrin Linnartz,
Dominik Lock,
Andrew Kaiser,
Christoph Herbel,
Dominik Eckardt,
Melina Lamorte,
Dorothee Lenhard,
Julia Schüler,
Philipp Ströbel,
Jeannine Missbach-Guentner,
Diana Pinkert-Leetsch,
Frauke Alves,
Andreas Bosio and
Olaf Hardt ()
Nature Communications, 2021, vol. 12, issue 1, 1-18 Abstract: Abstract A major roadblock prohibiting effective cellular immunotherapy of pancreatic ductal adenocarcinoma (PDAC) is the lack of suitable tumor-specific antigens. To address this challenge, here we combine flow cytometry screenings, bioinformatic expression analyses and a cyclic immunofluorescence platform. We identify CLA, CD66c, CD318 and TSPAN8 as target candidates among 371 antigens and generate 32 CARs specific for these molecules. CAR T cell activity is evaluated in vitro based on target cell lysis, T cell activation and cytokine release. Promising constructs are evaluated in vivo. CAR T cells specific for CD66c, CD318 and TSPAN8 demonstrate efficacies ranging from stabilized disease to complete tumor eradication with CD318 followed by TSPAN8 being the most promising candidates for clinical translation based on functionality and predicted safety profiles. This study reveals potential target candidates for CAR T cell based immunotherapy of PDAC together with a functional set of CAR constructs specific for these molecules. Date: 2021 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21774-4 Ordering information: This journal article can be ordered from DOI: 10.1038/s41467-021-21774-4 Access Statistics for this article Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie More articles in Nature Communications from Nature |
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