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

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.