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Avidity‐Based Selection of Tissue‐Specific CAR‐T Cells from a Combinatorial Cellular Library of CARs

Using T‐cell chimeric antigen receptors (CAR‐T) to activate and redirect T cells to tumors expressing the cognate antigen represents a powerful approach in cancer therapy. However, normal tissues with low expression of tumor‐associated antigens (TAAs) can be mistargeted, resulting in severe side eff...

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Autores principales: Ma, Peixiang, Ren, Ping, Zhang, Chuyue, Tang, Jiaxing, Yu, Zheng, Zhu, Xuekai, Fan, Kun, Li, Guanglei, Zhu, Wei, Sang, Wei, Min, Chenyu, Chen, Wenzhang, Huang, Xingxu, Yang, Guang, Lerner, Richard A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967050/
https://www.ncbi.nlm.nih.gov/pubmed/33747727
http://dx.doi.org/10.1002/advs.202003091
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author Ma, Peixiang
Ren, Ping
Zhang, Chuyue
Tang, Jiaxing
Yu, Zheng
Zhu, Xuekai
Fan, Kun
Li, Guanglei
Zhu, Wei
Sang, Wei
Min, Chenyu
Chen, Wenzhang
Huang, Xingxu
Yang, Guang
Lerner, Richard A.
author_facet Ma, Peixiang
Ren, Ping
Zhang, Chuyue
Tang, Jiaxing
Yu, Zheng
Zhu, Xuekai
Fan, Kun
Li, Guanglei
Zhu, Wei
Sang, Wei
Min, Chenyu
Chen, Wenzhang
Huang, Xingxu
Yang, Guang
Lerner, Richard A.
author_sort Ma, Peixiang
collection PubMed
description Using T‐cell chimeric antigen receptors (CAR‐T) to activate and redirect T cells to tumors expressing the cognate antigen represents a powerful approach in cancer therapy. However, normal tissues with low expression of tumor‐associated antigens (TAAs) can be mistargeted, resulting in severe side effects. An approach using a collection of T cells expressing a diverse, 10(6)‐member combinatorial cellular library of CARs, in which members can be specifically enriched based on avidity for cell membrane antigens, is reported. Using CD38 as the target antigen, an efficient and effective selection of CARs specifically recognizing CD38(+) tumor cells is demonstrated. These selected CAR‐T's produce cytokines known to be associated with T cell activation in a CD38 expression‐dependent manner. This avidity‐based selection endows the engineered T cells with minimal off‐tumor effects, while retaining robust antitumor efficacy both in vitro and in vivo. The described method may facilitate the application of CAR‐T therapy to TAAs previously considered undruggable.
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spelling pubmed-79670502021-03-19 Avidity‐Based Selection of Tissue‐Specific CAR‐T Cells from a Combinatorial Cellular Library of CARs Ma, Peixiang Ren, Ping Zhang, Chuyue Tang, Jiaxing Yu, Zheng Zhu, Xuekai Fan, Kun Li, Guanglei Zhu, Wei Sang, Wei Min, Chenyu Chen, Wenzhang Huang, Xingxu Yang, Guang Lerner, Richard A. Adv Sci (Weinh) Full Papers Using T‐cell chimeric antigen receptors (CAR‐T) to activate and redirect T cells to tumors expressing the cognate antigen represents a powerful approach in cancer therapy. However, normal tissues with low expression of tumor‐associated antigens (TAAs) can be mistargeted, resulting in severe side effects. An approach using a collection of T cells expressing a diverse, 10(6)‐member combinatorial cellular library of CARs, in which members can be specifically enriched based on avidity for cell membrane antigens, is reported. Using CD38 as the target antigen, an efficient and effective selection of CARs specifically recognizing CD38(+) tumor cells is demonstrated. These selected CAR‐T's produce cytokines known to be associated with T cell activation in a CD38 expression‐dependent manner. This avidity‐based selection endows the engineered T cells with minimal off‐tumor effects, while retaining robust antitumor efficacy both in vitro and in vivo. The described method may facilitate the application of CAR‐T therapy to TAAs previously considered undruggable. John Wiley and Sons Inc. 2021-01-29 /pmc/articles/PMC7967050/ /pubmed/33747727 http://dx.doi.org/10.1002/advs.202003091 Text en © 2021 The Authors. Published by Wiley‐VCH GmbH This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Papers
Ma, Peixiang
Ren, Ping
Zhang, Chuyue
Tang, Jiaxing
Yu, Zheng
Zhu, Xuekai
Fan, Kun
Li, Guanglei
Zhu, Wei
Sang, Wei
Min, Chenyu
Chen, Wenzhang
Huang, Xingxu
Yang, Guang
Lerner, Richard A.
Avidity‐Based Selection of Tissue‐Specific CAR‐T Cells from a Combinatorial Cellular Library of CARs
title Avidity‐Based Selection of Tissue‐Specific CAR‐T Cells from a Combinatorial Cellular Library of CARs
title_full Avidity‐Based Selection of Tissue‐Specific CAR‐T Cells from a Combinatorial Cellular Library of CARs
title_fullStr Avidity‐Based Selection of Tissue‐Specific CAR‐T Cells from a Combinatorial Cellular Library of CARs
title_full_unstemmed Avidity‐Based Selection of Tissue‐Specific CAR‐T Cells from a Combinatorial Cellular Library of CARs
title_short Avidity‐Based Selection of Tissue‐Specific CAR‐T Cells from a Combinatorial Cellular Library of CARs
title_sort avidity‐based selection of tissue‐specific car‐t cells from a combinatorial cellular library of cars
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967050/
https://www.ncbi.nlm.nih.gov/pubmed/33747727
http://dx.doi.org/10.1002/advs.202003091
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