Exhaustion of CAR T cells: potential causes and solutions
Abstract Chimeric antigen receptor (CAR) T cell therapy has attracted attention for its promising therapeutic effects on hematological malignancies. However, there are problems such as relapse during long-term follow-up and limited effect on solid tumors with this therapy. Exhaustion, which impairs...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03442-3 |
| _version_ | 1828223215603810304 |
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| author | Taku Kouro Hidetomo Himuro Tetsuro Sasada |
| author_facet | Taku Kouro Hidetomo Himuro Tetsuro Sasada |
| author_sort | Taku Kouro |
| collection | DOAJ |
| description | Abstract Chimeric antigen receptor (CAR) T cell therapy has attracted attention for its promising therapeutic effects on hematological malignancies. However, there are problems such as relapse during long-term follow-up and limited effect on solid tumors with this therapy. Exhaustion, which impairs in vivo persistence and killing activity of CAR T cells, is one of the causes of these issues. Depending on their structure of extracellular portion, some CARs induce tonic signals in the absence of ligand stimulation and induce exhaustion phenotype in CAR T cells. Analysis of these self-activating CARs is expected to provide key information for understanding and resolving CAR T cell exhaustion. In this review, we introduced examples of self-activating CARs and summarized their phenotypes to figure out how CAR T cell exhaustion occurs. Further, we aimed to review promising solutions to the CAR T cell exhaustion that hampers generalized application of CAR T cell therapy. |
| first_indexed | 2024-04-12T17:04:20Z |
| format | Article |
| id | doaj.art-72e4ca42188a4cb5977201c24dd5142a |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-12T17:04:20Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-72e4ca42188a4cb5977201c24dd5142a2022-12-22T03:23:59ZengBMCJournal of Translational Medicine1479-58762022-05-0120111010.1186/s12967-022-03442-3Exhaustion of CAR T cells: potential causes and solutionsTaku Kouro0Hidetomo Himuro1Tetsuro Sasada2Division of Cancer Immunotherapy, Kanagawa Cancer Center Research InstituteDivision of Cancer Immunotherapy, Kanagawa Cancer Center Research InstituteDivision of Cancer Immunotherapy, Kanagawa Cancer Center Research InstituteAbstract Chimeric antigen receptor (CAR) T cell therapy has attracted attention for its promising therapeutic effects on hematological malignancies. However, there are problems such as relapse during long-term follow-up and limited effect on solid tumors with this therapy. Exhaustion, which impairs in vivo persistence and killing activity of CAR T cells, is one of the causes of these issues. Depending on their structure of extracellular portion, some CARs induce tonic signals in the absence of ligand stimulation and induce exhaustion phenotype in CAR T cells. Analysis of these self-activating CARs is expected to provide key information for understanding and resolving CAR T cell exhaustion. In this review, we introduced examples of self-activating CARs and summarized their phenotypes to figure out how CAR T cell exhaustion occurs. Further, we aimed to review promising solutions to the CAR T cell exhaustion that hampers generalized application of CAR T cell therapy.https://doi.org/10.1186/s12967-022-03442-3Chimeric antigen receptorExhaustionTonic signalEngineered cellEpigenetics |
| spellingShingle | Taku Kouro Hidetomo Himuro Tetsuro Sasada Exhaustion of CAR T cells: potential causes and solutions Journal of Translational Medicine Chimeric antigen receptor Exhaustion Tonic signal Engineered cell Epigenetics |
| title | Exhaustion of CAR T cells: potential causes and solutions |
| title_full | Exhaustion of CAR T cells: potential causes and solutions |
| title_fullStr | Exhaustion of CAR T cells: potential causes and solutions |
| title_full_unstemmed | Exhaustion of CAR T cells: potential causes and solutions |
| title_short | Exhaustion of CAR T cells: potential causes and solutions |
| title_sort | exhaustion of car t cells potential causes and solutions |
| topic | Chimeric antigen receptor Exhaustion Tonic signal Engineered cell Epigenetics |
| url | https://doi.org/10.1186/s12967-022-03442-3 |
| work_keys_str_mv | AT takukouro exhaustionofcartcellspotentialcausesandsolutions AT hidetomohimuro exhaustionofcartcellspotentialcausesandsolutions AT tetsurosasada exhaustionofcartcellspotentialcausesandsolutions |