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Single-Cell Analysis of Target Antigens of CAR-T Reveals a Potential Landscape of “On-Target, Off-Tumor Toxicity”

Cellular immunotherapy represented by CD19-directed chimeric antigen receptor T (CAR-T) cells has achieved great success in recent years. An increasing number of CAR-T therapies are being developed for cancer treatment, but the frequent and varied adverse events, such as “on-target, off-tumor toxici...

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Autores principales: Zhang, Yinyin, Li, Yingmei, Cao, Weijie, Wang, Fang, Xie, Xinsheng, Li, Yadan, Wang, Xiaoyi, Guo, Rong, Jiang, Zhongxing, Guo, Rongqun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716389/
https://www.ncbi.nlm.nih.gov/pubmed/34975912
http://dx.doi.org/10.3389/fimmu.2021.799206
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author Zhang, Yinyin
Li, Yingmei
Cao, Weijie
Wang, Fang
Xie, Xinsheng
Li, Yadan
Wang, Xiaoyi
Guo, Rong
Jiang, Zhongxing
Guo, Rongqun
author_facet Zhang, Yinyin
Li, Yingmei
Cao, Weijie
Wang, Fang
Xie, Xinsheng
Li, Yadan
Wang, Xiaoyi
Guo, Rong
Jiang, Zhongxing
Guo, Rongqun
author_sort Zhang, Yinyin
collection PubMed
description Cellular immunotherapy represented by CD19-directed chimeric antigen receptor T (CAR-T) cells has achieved great success in recent years. An increasing number of CAR-T therapies are being developed for cancer treatment, but the frequent and varied adverse events, such as “on-target, off-tumor toxicity”, limit CAR-T application. Here, we identify the target antigen expression patterns of CAR therapies in 18 tissues and organs (peripheral blood mononuclear cells, bone marrow, lymph nodes, spleen, heart, ascending aortic tissue, trachea, lung, skin, kidney, bladder, esophagus, stomach, small intestine, rectum, liver, common bile duct, and pancreas) from healthy human samples. The atlas determines target antigens expressed on some normal cell types, which facilitates elucidating the cause of “on-target, off-tumor toxicity” in special tissues and organs by targeting some antigens, but not others. Moreover, we describe the target antigen expression patterns of B-lineage-derived malignant cells, acute myeloid leukemia (AML), and solid tumors. Overall, the present study indicates the pathogenesis of “on-target, off-tumor toxicity” during CAR therapies and provides guidance on taking preventive measures during CAR treatment.
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spelling pubmed-87163892021-12-31 Single-Cell Analysis of Target Antigens of CAR-T Reveals a Potential Landscape of “On-Target, Off-Tumor Toxicity” Zhang, Yinyin Li, Yingmei Cao, Weijie Wang, Fang Xie, Xinsheng Li, Yadan Wang, Xiaoyi Guo, Rong Jiang, Zhongxing Guo, Rongqun Front Immunol Immunology Cellular immunotherapy represented by CD19-directed chimeric antigen receptor T (CAR-T) cells has achieved great success in recent years. An increasing number of CAR-T therapies are being developed for cancer treatment, but the frequent and varied adverse events, such as “on-target, off-tumor toxicity”, limit CAR-T application. Here, we identify the target antigen expression patterns of CAR therapies in 18 tissues and organs (peripheral blood mononuclear cells, bone marrow, lymph nodes, spleen, heart, ascending aortic tissue, trachea, lung, skin, kidney, bladder, esophagus, stomach, small intestine, rectum, liver, common bile duct, and pancreas) from healthy human samples. The atlas determines target antigens expressed on some normal cell types, which facilitates elucidating the cause of “on-target, off-tumor toxicity” in special tissues and organs by targeting some antigens, but not others. Moreover, we describe the target antigen expression patterns of B-lineage-derived malignant cells, acute myeloid leukemia (AML), and solid tumors. Overall, the present study indicates the pathogenesis of “on-target, off-tumor toxicity” during CAR therapies and provides guidance on taking preventive measures during CAR treatment. Frontiers Media S.A. 2021-12-16 /pmc/articles/PMC8716389/ /pubmed/34975912 http://dx.doi.org/10.3389/fimmu.2021.799206 Text en Copyright © 2021 Zhang, Li, Cao, Wang, Xie, Li, Wang, Guo, Jiang and Guo https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhang, Yinyin
Li, Yingmei
Cao, Weijie
Wang, Fang
Xie, Xinsheng
Li, Yadan
Wang, Xiaoyi
Guo, Rong
Jiang, Zhongxing
Guo, Rongqun
Single-Cell Analysis of Target Antigens of CAR-T Reveals a Potential Landscape of “On-Target, Off-Tumor Toxicity”
title Single-Cell Analysis of Target Antigens of CAR-T Reveals a Potential Landscape of “On-Target, Off-Tumor Toxicity”
title_full Single-Cell Analysis of Target Antigens of CAR-T Reveals a Potential Landscape of “On-Target, Off-Tumor Toxicity”
title_fullStr Single-Cell Analysis of Target Antigens of CAR-T Reveals a Potential Landscape of “On-Target, Off-Tumor Toxicity”
title_full_unstemmed Single-Cell Analysis of Target Antigens of CAR-T Reveals a Potential Landscape of “On-Target, Off-Tumor Toxicity”
title_short Single-Cell Analysis of Target Antigens of CAR-T Reveals a Potential Landscape of “On-Target, Off-Tumor Toxicity”
title_sort single-cell analysis of target antigens of car-t reveals a potential landscape of “on-target, off-tumor toxicity”
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716389/
https://www.ncbi.nlm.nih.gov/pubmed/34975912
http://dx.doi.org/10.3389/fimmu.2021.799206
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