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CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma

BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is an aggressive lymphoma with a poor prognosis. Chimeric antigen receptor-transduced T (CAR-T) cell therapy has become a promising immunotherapeutic strategy against haematologic malignancies. METHODS: In this study, four CAR-T cell lines (CD38-CAR...

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Detalles Bibliográficos
Autores principales: Li, Hongwen, Song, Wenting, Wu, Jiazhuo, Shi, Zhuangzhuang, Gao, Yuyang, Li, Jiwei, Han, Lijuan, Zhang, Jianxiang, Li, Zhaoming, Li, Yong, Zhang, Mingzhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470138/
https://www.ncbi.nlm.nih.gov/pubmed/37649020
http://dx.doi.org/10.1186/s12916-023-03040-0
Descripción
Sumario:BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is an aggressive lymphoma with a poor prognosis. Chimeric antigen receptor-transduced T (CAR-T) cell therapy has become a promising immunotherapeutic strategy against haematologic malignancies. METHODS: In this study, four CAR-T cell lines (CD38-CAR, LMP1-CAR, CD38-LMP1 tandem CAR 1 and CD38-LMP1 tandem CAR 2) were generated. The effect of CAR-T cells against NKTCL cells was evaluated both in vitro and in vivo. Expression of T cell activation markers and cytokines produced by CAR-T cells were detected by flow cytometry. RESULTS: The four CAR-T cell lines could effectively eliminate malignant NKTCL cells. They could be activated and produce inflammatory cytokines in a target-dependent manner. In vivo tests showed that the CAR-T cells exhibited significant antitumour effects in a xenotransplanted NKTCL mouse model. CONCLUSIONS: In summary, four CAR-T cell lines exhibited significant cytotoxicity against NKTCL cells both in vitro and in vivo. These results indicated the effective therapeutic promise of CD38 and LMP1 CAR-T cells in NKTCL. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-023-03040-0.