Pre-depletion of TRBC1+ T cells promotes the therapeutic efficacy of anti-TRBC1 CAR-T for T-cell malignancies

Targeting T cell receptor β-chain constant region 1 (TRBC1) CAR-T could specifically kill TRBC1+ T-cell malignancies. However, over-expressed CARs on anti-TRBC1 CAR transduced TRBC1+ T cells (CAR-C1) bound to autologous TRBC1, masking TRBC1 from identification by other anti-TRBC1 CAR-T, and moreover...

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Autores principales: Zhang, Chaoting, Palashati, Heyilimu, Rong, Zhuona, Lin, Ningjing, Shen, Luyan, Liu, Ying, Li, Shance, Yu, Bentong, Yang, Wenjun, Lu, Zheming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Letter to the Editor
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679992/
https://www.ncbi.nlm.nih.gov/pubmed/33218364
http://dx.doi.org/10.1186/s12943-020-01282-7
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author Zhang, Chaoting
Palashati, Heyilimu
Rong, Zhuona
Lin, Ningjing
Shen, Luyan
Liu, Ying
Li, Shance
Yu, Bentong
Yang, Wenjun
Lu, Zheming
author_facet Zhang, Chaoting
Palashati, Heyilimu
Rong, Zhuona
Lin, Ningjing
Shen, Luyan
Liu, Ying
Li, Shance
Yu, Bentong
Yang, Wenjun
Lu, Zheming
author_sort Zhang, Chaoting
collection PubMed
description Targeting T cell receptor β-chain constant region 1 (TRBC1) CAR-T could specifically kill TRBC1+ T-cell malignancies. However, over-expressed CARs on anti-TRBC1 CAR transduced TRBC1+ T cells (CAR-C1) bound to autologous TRBC1, masking TRBC1 from identification by other anti-TRBC1 CAR-T, and moreover only the remaining unoccupied CARs recognized TRBC1+ cells, considerably reducing therapeutic potency of CAR-C1. In addition, co-culture of anti-TRBC1 CAR-T and TRBC1+ cells could promote exhaustion and terminal differentiation of CAR-T. These findings provide a rationale for pre-depleting TRBC1+ T cells before anti-TRBC1 CAR-T manufacturing. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-020-01282-7.
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spelling pubmed-76799922020-11-23 Pre-depletion of TRBC1+ T cells promotes the therapeutic efficacy of anti-TRBC1 CAR-T for T-cell malignancies Zhang, Chaoting Palashati, Heyilimu Rong, Zhuona Lin, Ningjing Shen, Luyan Liu, Ying Li, Shance Yu, Bentong Yang, Wenjun Lu, Zheming Mol Cancer Letter to the Editor Targeting T cell receptor β-chain constant region 1 (TRBC1) CAR-T could specifically kill TRBC1+ T-cell malignancies. However, over-expressed CARs on anti-TRBC1 CAR transduced TRBC1+ T cells (CAR-C1) bound to autologous TRBC1, masking TRBC1 from identification by other anti-TRBC1 CAR-T, and moreover only the remaining unoccupied CARs recognized TRBC1+ cells, considerably reducing therapeutic potency of CAR-C1. In addition, co-culture of anti-TRBC1 CAR-T and TRBC1+ cells could promote exhaustion and terminal differentiation of CAR-T. These findings provide a rationale for pre-depleting TRBC1+ T cells before anti-TRBC1 CAR-T manufacturing. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-020-01282-7. BioMed Central 2020-11-21 /pmc/articles/PMC7679992/ /pubmed/33218364 http://dx.doi.org/10.1186/s12943-020-01282-7 Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Letter to the Editor
Zhang, Chaoting
Palashati, Heyilimu
Rong, Zhuona
Lin, Ningjing
Shen, Luyan
Liu, Ying
Li, Shance
Yu, Bentong
Yang, Wenjun
Lu, Zheming
Pre-depletion of TRBC1+ T cells promotes the therapeutic efficacy of anti-TRBC1 CAR-T for T-cell malignancies
title Pre-depletion of TRBC1+ T cells promotes the therapeutic efficacy of anti-TRBC1 CAR-T for T-cell malignancies
title_full Pre-depletion of TRBC1+ T cells promotes the therapeutic efficacy of anti-TRBC1 CAR-T for T-cell malignancies
title_fullStr Pre-depletion of TRBC1+ T cells promotes the therapeutic efficacy of anti-TRBC1 CAR-T for T-cell malignancies
title_full_unstemmed Pre-depletion of TRBC1+ T cells promotes the therapeutic efficacy of anti-TRBC1 CAR-T for T-cell malignancies
title_short Pre-depletion of TRBC1+ T cells promotes the therapeutic efficacy of anti-TRBC1 CAR-T for T-cell malignancies
title_sort pre-depletion of trbc1+ t cells promotes the therapeutic efficacy of anti-trbc1 car-t for t-cell malignancies
topic Letter to the Editor
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679992/
https://www.ncbi.nlm.nih.gov/pubmed/33218364
http://dx.doi.org/10.1186/s12943-020-01282-7
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