Bibliographic Details
| Title: |
Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma. |
| Authors: |
Schäfer, Daniel, Tomiuk, Stefan, Küster, Laura N., Rawashdeh, Wa'el Al, Henze, Janina, Tischler-Höhle, German, Agorku, David J., Brauner, Janina, Linnartz, Cathrin, Lock, Dominik, Kaiser, Andrew, Herbel, Christoph, Eckardt, Dominik, Lamorte, Melina, Lenhard, Dorothee, Schüler, Julia, Ströbel, Philipp, Missbach-Guentner, Jeannine, Pinkert-Leetsch, Diana, Alves, Frauke |
| Source: |
Nature Communications; 3/5/2021, Vol. 12 Issue 1, p1-18, 18p |
| Subject Terms: |
T cells, AUTOMOBILES, LYSIS, IMMUNOTHERAPY, CYTOTOXIC T cells, ADENOCARCINOMA |
| 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. There is an unmet clinical need to identify therapeutic options for the treatment of pancreatic cancer (PDAC). Here the authors present a systematic screening approach for the identification of potential PDAC cell surface target candidates for CAR-T cell based immunotherapy, followed by their functional validation in preclinical models. [ABSTRACT FROM AUTHOR] |
|
Copyright of Nature Communications is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |
