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Single-cell analysis of the survival mechanisms of fratricidal CAR-T targeting of T cell malignancies.
Hu, Hui; Tang, Ling; Zhao, Yuyan; Cheng, Jiali; Huang, Mei; You, Yong; Zou, Ping; Lei, Qian; Zhu, Xiaojian; Guo, An-Yuan.
Afiliación
  • Hu H; Department of Hematology, West China Biomedical Big Data Center, West China Hospital, Med-X Center for Informatics, Sichuan University, Chengdu 610041, China.
  • Tang L; Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
  • Zhao Y; Department of Hematology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
  • Cheng J; Hubei Bioinformatics & Molecular Imaging Key Laboratory, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
  • Huang M; Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • You Y; Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • Zou P; Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  • Lei Q; Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  • Zhu X; Department of Hematology, West China Biomedical Big Data Center, West China Hospital, Med-X Center for Informatics, Sichuan University, Chengdu 610041, China.
  • Guo AY; Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Mol Ther Nucleic Acids ; 35(2): 102225, 2024 Jun 11.
Article en En | MEDLINE | ID: mdl-38948332
ABSTRACT
Chimeric antigen receptor T (CAR-T) cell therapy targeting T cell tumors still faces many challenges, one of which is its fratricide due to the target gene expressed on CAR-T cells. Despite this, these CAR-T cells can be expanded in vitro by extending the culture time and effectively eliminating malignant T cells. However, the mechanisms underlying CAR-T cell survival in cell subpopulations, the molecules involved, and their regulation are still unknown. We performed single-cell transcriptome profiling to investigate the fratricidal CAR-T products (CD26 CAR-Ts and CD44v6 CAR-Ts) targeting T cells, taking CD19 CAR-Ts targeting B cells from the same donor as a control. Compared with CD19 CAR-Ts, fratricidal CAR-T cells exhibit no unique cell subpopulation, but have more exhausted T cells, fewer cytotoxic T cells, and more T cell receptor (TCR) clonal amplification. Furthermore, we observed that fratricidal CAR-T cell survival was accompanied by target gene expression. Gene expression results suggest that fratricidal CAR-T cells may downregulate their human leukocyte antigen (HLA) molecules to evade T cell recognition. Single-cell regulatory network analysis and suppression experiments revealed that exhaustion mediated by critical regulatory factors may contribute to fratricidal CAR-T cell survival. Together, these data provide valuable and first-time insights into the survival of fratricidal CAR-T cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Nucleic Acids Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Nucleic Acids Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos