C-type lectin-like molecule-1 (CLL1) is preferentially expressed on acute myeloid leukemia (AML) stem cells and leukemic blasts, while showing limited expression on normal hematopoietic stem cells. This expression pattern makes CLL1 an attractive AML-associated antigen and a promising target for cellular immunotherapy. Preclinical studies have demonstrated that anti-CLL1 chimeric antigen receptor T (CAR-T) cells exhibit potent antitumor activity both in vitro and in AML xenograft mouse models, providing a strong rationale for clinical translation.

Building on these findings, investigators conducted a phase 1/2 clinical trial to evaluate autologous anti-CLL1 CAR-T cell therapy in pediatric patients with relapsed or refractory acute myeloid leukemia (R/R-AML), a population with limited treatment options and poor outcomes. Eight children with R/R-AML were enrolled in this study to assess the safety and preliminary efficacy of CLL1-targeted CAR-T therapy.

Following lymphodepletion conditioning, each patient received a single infusion of autologous anti-CLL1 CAR-T cells. The treatment was generally well tolerated. Cytokine release syndrome (CRS), a common toxicity associated with CAR-T therapy, was observed in all patients but remained limited to grade 1–2 severity. Importantly, no treatment-related deaths or life-threatening adverse events occurred, supporting the favorable safety profile of anti-CLL1 CAR-T therapy in this pediatric cohort.

Encouraging antileukemic activity was observed after CAR-T cell infusion. Four of the eight patients achieved a morphologic leukemia-free state (MLFS) with minimal residual disease (MRD) negativity. One patient achieved MLFS with persistent MRD positivity, while another reached complete remission with incomplete hematologic recovery (CRi) but remained MRD positive. One patient experienced partial remission, and one patient maintained stable disease; notably, this patient still demonstrated effective clearance of CLL1-positive AML blasts, indicating on-target biological activity of the CAR-T cells.

Collectively, these clinical outcomes suggest that anti-CLL1 CAR-T cell immunotherapy can induce meaningful responses in children with relapsed or refractory AML, including deep remissions in a subset of patients. Combined with its manageable toxicity profile, CLL1-targeted CAR-T therapy represents a promising and well-tolerated therapeutic option for pediatric R/R-AML.

This study highlights the potential of antigen-directed CAR-T strategies beyond CD19-positive malignancies and underscores GoBroad Healthcare Group's commitment to advancing innovative cellular immunotherapies for high-risk pediatric hematologic cancers through translational and clinical research.

Refer to the original: https://doi.org/10.1038/s41375-022-01703-0