Development and functional verification of CAR-T cells targeting CLL-1.
10.3760/cma.j.issn.0253-2727.2022.02.003
- VernacularTitle:靶向CLL-1嵌合抗原受体T细胞的构建及其功能验证
- Author:
Xiao CHAI
1
;
Xin JIN
1
;
Min Feng ZHAO
1
Author Information
1. Tianjin First Central Hospital, Tianjin 300192, China.
- Publication Type:Journal Article
- Keywords:
C-type lectin-like molecule 1;
Cell therapy;
Chimeric antigen receptor;
Leukemia, myeloid, acute
- MeSH:
Animals;
Cell Line, Tumor;
Cytokines;
Humans;
Immunotherapy, Adoptive;
Lectins, C-Type;
Leukemia, Myeloid, Acute/metabolism*;
Mice;
Receptors, Mitogen;
T-Lymphocytes
- From:
Chinese Journal of Hematology
2022;43(2):102-106
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the development of a CAR-T cells targeting CLL-1 and verify its function. Methods: The expression levels of CLL-1 targets in cell lines and primary cells were detected by flow cytometry. A CLL-1 CAR vector was constructed, and the corresponding lentivirus was prepared. After infection and activation of T cells, CAR-T cells targeting CLL-1 were produced and their function was verified in vitro and in vivo. Results: CLL-1 was expressed in acute myeloid leukemia (AML) cell lines and primary AML cells. The transduction rate of the prepared CAR T cells was 77.82%. In AML cell lines and AML primary cells, CLL-1-targeting CAR-T cells significantly and specifically killed CLL-1-expressing cells. Compared to untransduced T cells, CAR-T cells killed target cells and secreted inflammatory cytokines, such as interleukin-6 and interferon-γ, at significantly higher levels (P<0.001) . In an in vivo human xenograft mouse model of AML, CLL-1 CAR-T cells also exhibited potent antileukemic activity and induced prolonged mouse survival compared with untransduced T cells [not reached vs 22 days (95%CI 19-24 days) , P=0.002]. Conclusion: CAR-T cells targeting CLL-1 have been successfully produced and have excellent functions.
