Anti-CLL1 Chimeric Antigen Receptor T-Cell Therapy in Children with Relapsed/Refractory Acute Myeloid Leukemia

• Published in: Clinical cancer research Vol. 27; no. 13; pp. 3549 - 3555
• Main Authors: Zhang, Hui, Wang, Pengfei, Li, Zhuoyan, He, Yingyi, Gan, Wenting, Jiang, Hua
• Format: Journal Article
• Language: English
• Published: United States 01.07.2021
• Subjects: Cell- and Tissue-Based Therapy; Child; Humans; Immunotherapy, Adoptive - adverse effects; Leukemia, Myeloid, Acute - genetics; Leukocytes, Mononuclear; Receptors, Chimeric Antigen
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-20-4543

The survival rate of children with refractory/relapsed acute myeloid leukemia (R/R-AML) by salvage chemotherapy is minimal. Treatment with chimeric antigen receptor T cells (CAR T) has emerged as a novel therapy to improve malignancies treatment. C-type lectin-like molecule 1 (CLL1) is highly expressed on AML stem cells, blast cells, and monocytes, but not on normal hematopoietic stem cells, indicating the therapeutic potential of anti-CLL1 CAR T in AML treatment. This study aimed to test the safety and efficacy of CAR T-cell therapy in R/R-AML. Four pediatric patients with R/R-AML were enrolled in the ongoing phase I/II anti-CLL1 CAR T-cell therapy trial. The CAR design was based on an apoptosis-inducing gene, FKBP-caspase 9, to establish a safer CAR (4SCAR) application. Anti-CLL1 CAR was transduced into peripheral blood mononuclear cells of the patients via lentivector 4SCAR, followed by infusion into the recipients after lymphodepletion chemotherapy. Cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and other adverse events were documented. Treatment response was evaluated by morphology and flow cytometry-based minimal residual disease assays. Three patients with R/R-AML achieved complete remission and minimal residual disease negativity, while the other patient remained alive for 5 months. All these patients experienced low-grade and manageable adverse events. On the basis of our single-institution experience, autologous anti-CLL1 CAR T-cell therapy has the potential to be a safe and efficient alternative treatment for children with R/R-AML, and therefore requires further investigation.