Abstract: C-type lectin like molecule-1 (CLL1) is preferentially expressed on acute myeloid leukemia (AML) stem cells and AML blasts, and can be considered as AML-associated antigen. Anti-CLL1-based CAR-T cells exhibited effective tumor killing capacity in vitro and in AML-bearing mouse model. In this report, eight children with relapsed or refractory AML (R/R-AML) were recruited for a phase 1/2 clinical trial of autologous anti-CLL1 CAR-T cell immunotherapy. The objectives of this clinical trial were to evaluate the safety and the anti-AML responses after CLL1-CAR-T cell treatment, with long-term prognosis within those patients who did not receive allogeneic hematopoietic stem cells transplantation (allo-HSCT) as an additional aim. These R/R-AML patients received one dose of autologous CLL1-CAR-T cells after lymphodepletion conditioning. Grade 34 hematologic adverse events were observed post CAR-T cell infusion. Meanwhile, grade 12 cytokine release syndrome (CRS) was observed but without any lethal events. 4 out of 8 AML patients achieved incomplete remission (CRi) and minimal residual disease (MRD) negativity, 2 patients with CRi but MRD positivity, and 2 patients with decreased AML burden and CLL1 positive AML blast clearance. These results suggested that anti-CLL1-based CAR-T cell immunotherapy can be considered as a well-tolerated and effective option for treating children with R/R-AML.

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Characteristics of anti-CLL1 based CAR-T therapy for children with relapsed or refractory acute myeloid leukemia: the multi-center efficacy and safety...