Clinical Study on the Safety, Efficacy and Pharmacokinetics of Universal CLL1 Chimeric Antigen Receptor T-Cell in Relapsed/Refractory Acute Myeloid Leukemia

Summary

Acute myeloid leukemia (AML) is a common type of acute leukemia in adults. Although the treatment of AML has improved in recent decades, the 5-year survival rate remains below 50% due to the chemoresistance or toxicity of these treatments. Most patients eventually die from relapse and/or progressive disease, and these patients urgently need new treatment strategies. Chimeric antigen receptor T-cell (CAR-T cell) therapy is an adoptive immunotherapy that expresses one or more specific chimeric antigen receptors (CARs) on T cells through genetic engineering, enabling them to target tumor cells. CAR-T cell immunotherapy has been a milestone in tumor immunotherapy in recent years and has achieved remarkable efficacy in the treatment of hematological malignancies. Human C-type lectin-like molecule 1 (CLL-1) is specifically expressed on the tumor cells of more than 90% of AML patients. CLL1 is selectively expressed on the surface of leukemia stem cells but not on normal hematopoietic stem cells, making it an ideal target for AML. Autologous CLL1 CAR-T cells have shown strong therapeutic effects in previous studies. However, autologous CAR-T cells have disadvantages such as long preparation time and high cost. Universal CAR-T cells have effectively solved this problem. In this study, universal CAR-T cells targeting the CLL1 target were prepared based on the non-gene editing intracellular membrane protein retention technology, further expanding the application of CAR-T in the treatment of acute myeloid leukemia.

Timeline

Start

2026-02

Primary completion

2028-12

Completion

2028-12-12

Publications

• Results Liu J, Zhang Y, Guo R, Zhao Y, Sun R, Guo S, Lu W, Zhao M. Targeted CD7 CAR T-cells for treatment of T-Lymphocyte leukemia and lymphoma and acute myeloid leukemia: recent advances. Front Immunol. 2023 May 5;14:1170968. doi: 10.3389/fimmu.2023.1170968. eCollection 2023.
• Results Zhao Y, Bai X, Guo S, Zhang X, Liu J, Zhao M, Xie T, Meng H, Zhang Y, He X, Zhao M. Efficacy and safety of CAR-T therapy targeting CLL1 in patients with extramedullary diseases of acute myeloid leukemia. J Transl Med. 2024 Oct 2;22(1):888. doi: 10.1186/s12967-024-05705-7.
• Results Jin X, Zhang M, Sun R, Lyu H, Xiao X, Zhang X, Li F, Xie D, Xiong X, Wang J, Lu W, Zhang H, Zhao M. First-in-human phase I study of CLL-1 CAR-T cells in adults with relapsed/refractory acute myeloid leukemia. J Hematol Oncol. 2022 Jul 7;15(1):88. doi: 10.1186/s13045-022-01308-1.
• Results Wagner DL, Fritsche E, Pulsipher MA, Ahmed N, Hamieh M, Hegde M, Ruella M, Savoldo B, Shah NN, Turtle CJ, Wayne AS, Abou-El-Enein M. Immunogenicity of CAR T cells in cancer therapy. Nat Rev Clin Oncol. 2021 Jun;18(6):379-393. doi: 10.1038/s41571-021-00476-2. Epub 2021 Feb 25.
• Results Kantarjian H, Kadia T, DiNardo C, Daver N, Borthakur G, Jabbour E, Garcia-Manero G, Konopleva M, Ravandi F. Acute myeloid leukemia: current progress and future directions. Blood Cancer J. 2021 Feb 22;11(2):41. doi: 10.1038/s41408-021-00425-3.

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Indications