Cargando…
Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma
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....
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935963/ https://www.ncbi.nlm.nih.gov/pubmed/33674603 http://dx.doi.org/10.1038/s41467-021-21774-4 |
_version_ | 1783661107328581632 |
---|---|
author | 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 Bosio, Andreas Hardt, Olaf |
author_facet | 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 Bosio, Andreas Hardt, Olaf |
author_sort | Schäfer, Daniel |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7935963 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-79359632021-03-21 Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma 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 Bosio, Andreas Hardt, Olaf Nat Commun Article 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. Nature Publishing Group UK 2021-03-05 /pmc/articles/PMC7935963/ /pubmed/33674603 http://dx.doi.org/10.1038/s41467-021-21774-4 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article 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 Bosio, Andreas Hardt, Olaf Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma |
title | Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma |
title_full | Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma |
title_fullStr | Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma |
title_full_unstemmed | Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma |
title_short | Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma |
title_sort | identification of cd318, tspan8 and cd66c as target candidates for car t cell based immunotherapy of pancreatic adenocarcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935963/ https://www.ncbi.nlm.nih.gov/pubmed/33674603 http://dx.doi.org/10.1038/s41467-021-21774-4 |
work_keys_str_mv | AT schaferdaniel identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT tomiukstefan identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT kusterlauran identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT rawashdehwaelal identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT henzejanina identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT tischlerhohlegerman identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT agorkudavidj identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT braunerjanina identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT linnartzcathrin identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT lockdominik identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT kaiserandrew identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT herbelchristoph identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT eckardtdominik identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT lamortemelina identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT lenharddorothee identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT schulerjulia identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT strobelphilipp identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT missbachguentnerjeannine identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT pinkertleetschdiana identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT alvesfrauke identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT bosioandreas identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma AT hardtolaf identificationofcd318tspan8andcd66castargetcandidatesforcartcellbasedimmunotherapyofpancreaticadenocarcinoma |