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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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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. |
format | Online Article Text |
id | pubmed-7967050 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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