Activation-induced cell death in CAR-T cell therapy
Engineered T cells expressing chimeric antigen receptors (CARs) with tumor specificity have shown remarkable therapeutic effects on hematologic malignancies. However, CAR-T cells are less effective on solid tumors mainly due to the weak persistence of CAR-T cells, which might be caused by T cell dea...
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| Veröffentlicht in: | Human cell : official journal of Human Cell Research Society 2022-03, Vol.35 (2), p.441-447 |
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| container_title | Human cell : official journal of Human Cell Research Society |
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| creator | Huan, Tian Chen, Dongfeng Liu, Guodong Zhang, Hailing Wang, Xiaoyan Wu, Zhi Wu, Yan Xu, Qinggang Yu, Feng |
| description | Engineered T cells expressing chimeric antigen receptors (CARs) with tumor specificity have shown remarkable therapeutic effects on hematologic malignancies. However, CAR-T cells are less effective on solid tumors mainly due to the weak persistence of CAR-T cells, which might be caused by T cell death. Significant activation-induced cell death (AICD) of CAR-T cells was triggered by repeated antigen stimulation. AICD of T cell is characterized by the upregulation of death receptors and low persistence of T cells. Understanding the mechanism of AICD is crucial to improve the anti-tumor effect of CAR-T cells against solid tumors. Many approaches have been applied in CAR-T cell modification to enhance their anti-apoptosis ability. In this review, we summarized the molecular mechanisms of AICD in CAR-T cells and the progresses of anti-AICD in CAR-T cells therapy. |
| doi_str_mv | 10.1007/s13577-022-00670-z |
| format | Article |
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However, CAR-T cells are less effective on solid tumors mainly due to the weak persistence of CAR-T cells, which might be caused by T cell death. Significant activation-induced cell death (AICD) of CAR-T cells was triggered by repeated antigen stimulation. AICD of T cell is characterized by the upregulation of death receptors and low persistence of T cells. Understanding the mechanism of AICD is crucial to improve the anti-tumor effect of CAR-T cells against solid tumors. Many approaches have been applied in CAR-T cell modification to enhance their anti-apoptosis ability. In this review, we summarized the molecular mechanisms of AICD in CAR-T cells and the progresses of anti-AICD in CAR-T cells therapy.</description><identifier>ISSN: 1749-0774</identifier><identifier>ISSN: 0914-7470</identifier><identifier>EISSN: 1749-0774</identifier><identifier>DOI: 10.1007/s13577-022-00670-z</identifier><identifier>PMID: 35032297</identifier><language>eng</language><publisher>Singapore: Springer Singapore</publisher><subject>Antigens ; Apoptosis ; Biomedical and Life Sciences ; Cell activation ; Cell Biology ; Cell Death ; Cell therapy ; Cell- and Tissue-Based Therapy ; Chimeric antigen receptors ; Death receptors ; Gynecology ; Humans ; Immunotherapy, Adoptive ; Life Sciences ; Lymphocytes ; Lymphocytes T ; Molecular modelling ; Neoplasms - therapy ; Oncology ; Receptors, Chimeric Antigen - genetics ; Receptors, Chimeric Antigen - metabolism ; Reproductive Medicine ; Review Article ; Solid tumors ; Stem Cells ; Surgery ; T-Lymphocytes - metabolism ; Tumors</subject><ispartof>Human cell : official journal of Human Cell Research Society, 2022-03, Vol.35 (2), p.441-447</ispartof><rights>The Author(s) under exclusive licence to Japan Human Cell Society 2022</rights><rights>2022. 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However, CAR-T cells are less effective on solid tumors mainly due to the weak persistence of CAR-T cells, which might be caused by T cell death. Significant activation-induced cell death (AICD) of CAR-T cells was triggered by repeated antigen stimulation. AICD of T cell is characterized by the upregulation of death receptors and low persistence of T cells. Understanding the mechanism of AICD is crucial to improve the anti-tumor effect of CAR-T cells against solid tumors. Many approaches have been applied in CAR-T cell modification to enhance their anti-apoptosis ability. In this review, we summarized the molecular mechanisms of AICD in CAR-T cells and the progresses of anti-AICD in CAR-T cells therapy.</description><subject>Antigens</subject><subject>Apoptosis</subject><subject>Biomedical and Life Sciences</subject><subject>Cell activation</subject><subject>Cell Biology</subject><subject>Cell Death</subject><subject>Cell therapy</subject><subject>Cell- and Tissue-Based Therapy</subject><subject>Chimeric antigen receptors</subject><subject>Death receptors</subject><subject>Gynecology</subject><subject>Humans</subject><subject>Immunotherapy, Adoptive</subject><subject>Life Sciences</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Molecular modelling</subject><subject>Neoplasms - therapy</subject><subject>Oncology</subject><subject>Receptors, Chimeric Antigen - genetics</subject><subject>Receptors, Chimeric Antigen - metabolism</subject><subject>Reproductive Medicine</subject><subject>Review Article</subject><subject>Solid tumors</subject><subject>Stem Cells</subject><subject>Surgery</subject><subject>T-Lymphocytes - metabolism</subject><subject>Tumors</subject><issn>1749-0774</issn><issn>0914-7470</issn><issn>1749-0774</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLAzEQx4Motla_gAdZ8BxNMnk0x1KsCgVB6jmkSdZu2e7WZFdoP72rWx8nTzPM_B_wQ-iSkhtKiLpNFIRSmDCGCZGK4P0RGlLFNSZK8eM_-wCdpbQmhAsu2SkagCDAmFZDBBPXFO-2KeoKF5VvXfCZC2WZ-WCbVVZU2XTyjBf9rVmFaLe7c3SS2zKFi8McoZfZ3WL6gOdP94_TyRw7kLLB1PkltSJwZbUdBwYcQHoKwYLjLOfeCq4lJ0ILlTs6VjKXygtNKEDQlMEIXfe521i_tSE1Zl23seoqDZPA6FiC0p2K9SoX65RiyM02Fhsbd4YS88nJ9JxMx8l8cTL7znR1iG6Xm-B_LN9gOgH0gtS9qtcQf7v_if0A301wyA</recordid><startdate>20220301</startdate><enddate>20220301</enddate><creator>Huan, Tian</creator><creator>Chen, Dongfeng</creator><creator>Liu, Guodong</creator><creator>Zhang, Hailing</creator><creator>Wang, Xiaoyan</creator><creator>Wu, Zhi</creator><creator>Wu, Yan</creator><creator>Xu, Qinggang</creator><creator>Yu, Feng</creator><general>Springer Singapore</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0002-1929-3881</orcidid></search><sort><creationdate>20220301</creationdate><title>Activation-induced cell death in CAR-T cell therapy</title><author>Huan, Tian ; Chen, Dongfeng ; Liu, Guodong ; Zhang, Hailing ; Wang, Xiaoyan ; Wu, Zhi ; Wu, Yan ; Xu, Qinggang ; Yu, Feng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c366t-1cdb1a5e47a9a8e234336d13ea3c42f4da5496405957fc1876f67d590133e9123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antigens</topic><topic>Apoptosis</topic><topic>Biomedical and Life Sciences</topic><topic>Cell activation</topic><topic>Cell Biology</topic><topic>Cell Death</topic><topic>Cell therapy</topic><topic>Cell- and Tissue-Based Therapy</topic><topic>Chimeric antigen receptors</topic><topic>Death receptors</topic><topic>Gynecology</topic><topic>Humans</topic><topic>Immunotherapy, Adoptive</topic><topic>Life Sciences</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Molecular modelling</topic><topic>Neoplasms - therapy</topic><topic>Oncology</topic><topic>Receptors, Chimeric Antigen - genetics</topic><topic>Receptors, Chimeric Antigen - metabolism</topic><topic>Reproductive Medicine</topic><topic>Review Article</topic><topic>Solid tumors</topic><topic>Stem Cells</topic><topic>Surgery</topic><topic>T-Lymphocytes - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huan, Tian</creatorcontrib><creatorcontrib>Chen, Dongfeng</creatorcontrib><creatorcontrib>Liu, Guodong</creatorcontrib><creatorcontrib>Zhang, Hailing</creatorcontrib><creatorcontrib>Wang, Xiaoyan</creatorcontrib><creatorcontrib>Wu, Zhi</creatorcontrib><creatorcontrib>Wu, Yan</creatorcontrib><creatorcontrib>Xu, Qinggang</creatorcontrib><creatorcontrib>Yu, Feng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Human cell : official journal of Human Cell Research Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huan, Tian</au><au>Chen, Dongfeng</au><au>Liu, Guodong</au><au>Zhang, Hailing</au><au>Wang, Xiaoyan</au><au>Wu, Zhi</au><au>Wu, Yan</au><au>Xu, Qinggang</au><au>Yu, Feng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation-induced cell death in CAR-T cell therapy</atitle><jtitle>Human cell : official journal of Human Cell Research Society</jtitle><stitle>Human Cell</stitle><addtitle>Hum Cell</addtitle><date>2022-03-01</date><risdate>2022</risdate><volume>35</volume><issue>2</issue><spage>441</spage><epage>447</epage><pages>441-447</pages><issn>1749-0774</issn><issn>0914-7470</issn><eissn>1749-0774</eissn><abstract>Engineered T cells expressing chimeric antigen receptors (CARs) with tumor specificity have shown remarkable therapeutic effects on hematologic malignancies. 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| subjects | Antigens Apoptosis Biomedical and Life Sciences Cell activation Cell Biology Cell Death Cell therapy Cell- and Tissue-Based Therapy Chimeric antigen receptors Death receptors Gynecology Humans Immunotherapy, Adoptive Life Sciences Lymphocytes Lymphocytes T Molecular modelling Neoplasms - therapy Oncology Receptors, Chimeric Antigen - genetics Receptors, Chimeric Antigen - metabolism Reproductive Medicine Review Article Solid tumors Stem Cells Surgery T-Lymphocytes - metabolism Tumors |
| title | Activation-induced cell death in CAR-T cell therapy |
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