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Direct comparison of target-reactivity and cross-reactivity induced by CAR- and BiTE-redirected T cells for the development of antibody-based T-cell therapy

The development of chimeric antigen receptor (CAR) and bispecific T-cell engager (BiTE) has led to the successful application of cancer immunotherapy. The potential reactivity mediated by CAR- and BiTE-redirected T cells needs to be assessed to facilitate the application of these treatment options t...

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Autores principales: Maruta, Masaki, Ochi, Toshiki, Tanimoto, Kazushi, Asai, Hiroaki, Saitou, Takashi, Fujiwara, Hiroshi, Imamura, Takeshi, Takenaka, Katsuto, Yasukawa, Masaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746725/
https://www.ncbi.nlm.nih.gov/pubmed/31527633
http://dx.doi.org/10.1038/s41598-019-49834-2
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author Maruta, Masaki
Ochi, Toshiki
Tanimoto, Kazushi
Asai, Hiroaki
Saitou, Takashi
Fujiwara, Hiroshi
Imamura, Takeshi
Takenaka, Katsuto
Yasukawa, Masaki
author_facet Maruta, Masaki
Ochi, Toshiki
Tanimoto, Kazushi
Asai, Hiroaki
Saitou, Takashi
Fujiwara, Hiroshi
Imamura, Takeshi
Takenaka, Katsuto
Yasukawa, Masaki
author_sort Maruta, Masaki
collection PubMed
description The development of chimeric antigen receptor (CAR) and bispecific T-cell engager (BiTE) has led to the successful application of cancer immunotherapy. The potential reactivity mediated by CAR- and BiTE-redirected T cells needs to be assessed to facilitate the application of these treatment options to a broader range of patients. Here, we have generated CAR and BiTE possessing the same single chain fragment variable (scFv) specific for the HLA-A2/NY-ESO-1(157-165) complex (A2/NY-ESO-1(157)). Using HLA-A2(+)NY-ESO-1(+) myeloma cells and peptides presented by HLA-A2 molecules as a model, both sets of redirected T cells recognized and killed HLA-A2(+)NY-ESO-1(+) myeloma cells in an A2/NY-ESO-1(157)-specific manner in vitro. Moreover, CAR- and BiTE-activated T cells showed similar functional avidity, as assessed by cytokine production and killing activity, both displaying antitumor reactivity against HLA-A2(+)NY-ESO-1(+) myeloma cells in vivo. Interestingly, cross-reactivity for homologous peptides presented by HLA-A*02:01 and NY-ESO-1(157) peptide presented by HLA-A2 alleles was not identical between CAR- and BiTE-redirected T cells, probably due to structural differences of modified antibodies. These results have demonstrated that both antitumor CAR- and BiTE-activated T cells have comparable potential to recognize tumors, while paying attention to unknown off-target reactivity that would differ for each antibody-based modality even if the same scFv was employed.
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spelling pubmed-67467252019-09-27 Direct comparison of target-reactivity and cross-reactivity induced by CAR- and BiTE-redirected T cells for the development of antibody-based T-cell therapy Maruta, Masaki Ochi, Toshiki Tanimoto, Kazushi Asai, Hiroaki Saitou, Takashi Fujiwara, Hiroshi Imamura, Takeshi Takenaka, Katsuto Yasukawa, Masaki Sci Rep Article The development of chimeric antigen receptor (CAR) and bispecific T-cell engager (BiTE) has led to the successful application of cancer immunotherapy. The potential reactivity mediated by CAR- and BiTE-redirected T cells needs to be assessed to facilitate the application of these treatment options to a broader range of patients. Here, we have generated CAR and BiTE possessing the same single chain fragment variable (scFv) specific for the HLA-A2/NY-ESO-1(157-165) complex (A2/NY-ESO-1(157)). Using HLA-A2(+)NY-ESO-1(+) myeloma cells and peptides presented by HLA-A2 molecules as a model, both sets of redirected T cells recognized and killed HLA-A2(+)NY-ESO-1(+) myeloma cells in an A2/NY-ESO-1(157)-specific manner in vitro. Moreover, CAR- and BiTE-activated T cells showed similar functional avidity, as assessed by cytokine production and killing activity, both displaying antitumor reactivity against HLA-A2(+)NY-ESO-1(+) myeloma cells in vivo. Interestingly, cross-reactivity for homologous peptides presented by HLA-A*02:01 and NY-ESO-1(157) peptide presented by HLA-A2 alleles was not identical between CAR- and BiTE-redirected T cells, probably due to structural differences of modified antibodies. These results have demonstrated that both antitumor CAR- and BiTE-activated T cells have comparable potential to recognize tumors, while paying attention to unknown off-target reactivity that would differ for each antibody-based modality even if the same scFv was employed. Nature Publishing Group UK 2019-09-16 /pmc/articles/PMC6746725/ /pubmed/31527633 http://dx.doi.org/10.1038/s41598-019-49834-2 Text en © The Author(s) 2019 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
Maruta, Masaki
Ochi, Toshiki
Tanimoto, Kazushi
Asai, Hiroaki
Saitou, Takashi
Fujiwara, Hiroshi
Imamura, Takeshi
Takenaka, Katsuto
Yasukawa, Masaki
Direct comparison of target-reactivity and cross-reactivity induced by CAR- and BiTE-redirected T cells for the development of antibody-based T-cell therapy
title Direct comparison of target-reactivity and cross-reactivity induced by CAR- and BiTE-redirected T cells for the development of antibody-based T-cell therapy
title_full Direct comparison of target-reactivity and cross-reactivity induced by CAR- and BiTE-redirected T cells for the development of antibody-based T-cell therapy
title_fullStr Direct comparison of target-reactivity and cross-reactivity induced by CAR- and BiTE-redirected T cells for the development of antibody-based T-cell therapy
title_full_unstemmed Direct comparison of target-reactivity and cross-reactivity induced by CAR- and BiTE-redirected T cells for the development of antibody-based T-cell therapy
title_short Direct comparison of target-reactivity and cross-reactivity induced by CAR- and BiTE-redirected T cells for the development of antibody-based T-cell therapy
title_sort direct comparison of target-reactivity and cross-reactivity induced by car- and bite-redirected t cells for the development of antibody-based t-cell therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746725/
https://www.ncbi.nlm.nih.gov/pubmed/31527633
http://dx.doi.org/10.1038/s41598-019-49834-2
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