This is a phase 1, first-in-human (FIH), open-label, multicohort study to evaluate the safety, tolerability and preliminary efficacy of CLL1 or CD33 target Chimeric antigen receptor (CAR) -induced pluripotent stem cells derived NK cells in patients with relapsed/refractory AML

开始日期2024-04-30

申办/合作机构

浙江大学

[+1]

NCT05987696 / Not yet recruiting临床1期IIT

Phase I Study to Evaluate the Safety and Efficacy of NK Cell Therapy in Acute Myeloid Leukemia (AML).

This is a phase 1, first-in-human (FIH), open-label, multicohort study to evaluate the safety, tolerability and preliminary efficacy of iPSC NK cells in patients with relapsed/refractory AML or AML Minimal Residual Disease (MRD).

开始日期2023-08-10

申办/合作机构

杭州启函生物科技有限公司初创企业

100 项与 CD33/CLL1 dual CAR-NK cells(Hangzhou Qihan Biotech) 相关的临床结果

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100 项与 CD33/CLL1 dual CAR-NK cells(Hangzhou Qihan Biotech) 相关的转化医学

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100 项与 CD33/CLL1 dual CAR-NK cells(Hangzhou Qihan Biotech) 相关的专利（医药）

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项与 CD33/CLL1 dual CAR-NK cells(Hangzhou Qihan Biotech) 相关的文献（医药）

2024-08-06·Blood transfusion = Trasfusione del sangue

The tandem CD33-CLL1 CAR-T as an approach to treat acute myeloid leukemia.

Article

作者: Zhu, Yanliang ; Zhou, Li ; Zhou, Ziwei ; Nian, Zhigang ; Wu, Shu ; Feng, Shanglong ; Zhang, Yafeng ; Lu, Xueqin ; Peng, Peng ; Wang, Huiru

BACKGROUNDAcute myeloid leukemia (AML) is characterized by high heterogeneity, poor long-term survival, and a propensity for relapse. Exceptional efficacy in treating recurrent or refractory B-lymphoid malignancies has been demonstrated by Chimeric antigen receptor T cells (CAR-T cells). Given the therapeutic potential of targeting both CD33 and C-type lectin-like molecule-1 (CLL1) in AML, the development of a dual-targeting CD33-CLL1 CAR-T cells assumes significant importance.MATERIALS AND METHODSThe expressions of CD33 and CLL-1 antigens in peripheral blood cells and bone marrow cells from AML patients was assessed. Subsequently, a Chimeric Antigen Receptor (CAR) incorporating a dual-specific single-chain variable fragment targeting CLL1 and CD33 (CD33-CLL1-CAR-T) was engineered. The anti-tumor efficacy and potential side effects of CD33-CLL1-CAR-T cells were comprehensively investigated in both in vitro and in vivo settings.RESULTSThe constructed tandem CD33-CLL1 CAR-T exhibited potent cytotoxicity against leukemia cell lines and human primary AML cells in vitro. Co-cultivation of AML blasts with CD33-CLL1-CAR-T cells resulted in effective proliferation and the secretion of substantial quantities of GM-CSF and IFN-γ. Importantly, the impact of CD33-CLL1-CAR-T cells on normal hematopoietic stem cells was minimal, ensuring safety in vivo mouse models. Notably, significant anti-leukemic activity was observed in the mouse model, with CD33-CLL1-CAR-T cells leading to tumor eradication and prolonged survival.DISCUSSIONThe tandem CD33-CLL1 CAR-T cells not only efficiently eliminated AML blasts but also exhibited low cytotoxicity toward normal hematopoietic stem cells (HSCs). These findings underscore the potential clinical applicability of the tandem CD33-CLL1 CAR-T cells as an effective and safe treatment strategy for AML, representing a noteworthy advancement in the field of CAR-T cells therapy.

100 项与 CD33/CLL1 dual CAR-NK cells(Hangzhou Qihan Biotech) 相关的药物交易

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