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Development and functional verification of CAR-T cells targeting CLL-1 / 中华血液学杂志
Chinese Journal of Hematology ; (12): 102-106, 2022.
Article in Chinese | WPRIM | ID: wpr-929540
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.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Receptors, Mitogen / T-Lymphocytes / Leukemia, Myeloid, Acute / Cytokines / Immunotherapy, Adoptive / Lectins, C-Type / Cell Line, Tumor Limits: Animals / Humans Language: Chinese Journal: Chinese Journal of Hematology Year: 2022 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Receptors, Mitogen / T-Lymphocytes / Leukemia, Myeloid, Acute / Cytokines / Immunotherapy, Adoptive / Lectins, C-Type / Cell Line, Tumor Limits: Animals / Humans Language: Chinese Journal: Chinese Journal of Hematology Year: 2022 Type: Article