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

Autor:	Wang H; Department of Blood Transfusion, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, HefeiChina., Feng S; Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, HefeiChina.; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China., Zhu Y; Nanjing Legend Biotechnology Co., Nanjing, China., Zhang Y; Nanjing Legend Biotechnology Co., Nanjing, China., Zhou Z; Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China., Nian Z; Institute of Immunology, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China., Lu X; Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China., Peng P; Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China., Wu S; Nanjing Legend Biotechnology Co., Nanjing, China., Zhou L; Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, HefeiChina.; Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Jazyk:	angličtina
Zdroj:	Blood transfusion = Trasfusione del sangue [Blood Transfus] 2024 Aug 06. Date of Electronic Publication: 2024 Aug 06.
DOI:	10.2450/BloodTransfus.786
Abstrakt:	Background: Acute 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 Methods: The 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. Results: The 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. Discussion: The 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.
Databáze:	MEDLINE
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