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T cell receptor β-chain-targeting chimeric antigen receptor T cells against T cell malignancies

The success of chimeric antigen receptor (CAR) T cells in treating B cell malignancies comes at the price of eradicating normal B cells. Even though T cell malignancies are aggressive and treatment options are limited, similar strategies for T cell malignancies are constrained by the severe immune s...

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Detalles Bibliográficos
Autores principales: Li, Fanlin, Zhang, Huihui, Wang, Wanting, Yang, Puyuan, Huang, Yue, Zhang, Junshi, Yan, Yaping, Wang, Yuan, Ding, Xizhong, Liang, Jie, Qi, Xinyue, Li, Min, Han, Ping, Zhang, Xiaoqing, Wang, Xin, Cao, Jiang, Fu, Yang-Xin, Yang, Xuanming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325690/
https://www.ncbi.nlm.nih.gov/pubmed/35882880
http://dx.doi.org/10.1038/s41467-022-32092-8
Descripción
Sumario:The success of chimeric antigen receptor (CAR) T cells in treating B cell malignancies comes at the price of eradicating normal B cells. Even though T cell malignancies are aggressive and treatment options are limited, similar strategies for T cell malignancies are constrained by the severe immune suppression arising from bystander T cell aplasia. Here, we show the selective killing of malignant T cells without affecting normal T cell-mediated immune responses in vitro and in a mouse model of disseminated leukemia. Further, we develop a CAR construct that carries the single chain variable fragment of a subtype-specific antibody against the variable TCR β-chain region. We demonstrate that these anti-Vβ8 CAR-T cells are able to recognize and kill all Vβ8(+) malignant T cells that arise from clonal expansion while sparing malignant or healthy Vβ8(−) T cells, allowing sufficient T cell-mediated cellular immunity. In summary, we present a proof of concept for a selective CAR-T cell therapy to eradicate T cell malignancies while maintaining functional adaptive immunity, which opens the possibility for clinical development.