Anti‐CLL1‐based CAR T‐cells with 4‐1‐BB or CD28/CD27 stimulatory domains in treating childhood refractory/relapsed acute myeloid leukemia

• Published in: Cancer medicine (Malden, MA) Vol. 12; no. 8; pp. 9655 - 9661
• Main Authors: Pei, Kunlin, Xu, Haoyu, Wang, Pengfei, Gan, Wening, Hu, Zhengbin, Su, Xiaoling, Zhang, Hui, He, Yingyi
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.04.2023; John Wiley and Sons Inc; Wiley
• Subjects: 4‐1‐BB; Acute myeloid leukemia; Antigens; anti‐CLL1 CAR T cells; Brief Communication; CD27 antigen; CD28 antigen; CD28 Antigens; CD28/CD27; Chemotherapy; Child; Childhood; Children; Cytokines; Drug resistance; Graft versus host disease; Humans; Immunotherapy, Adoptive - adverse effects; Infections; Leukemia; Leukemia, Myeloid, Acute - therapy; Lymphocytes T; Myeloproliferative Disorders; Neurotoxicity; Patients; Pediatrics; refractory/relapsed; T-Lymphocytes; Transplants & implants; Viral infections; 4-1-BB; refractory/relapsed; anti-CLL1 CAR T cells; CD28/CD27; acute myeloid leukemia
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.5916

Background Though the efficacy of anti C‐type lectin‐like molecule‐1 (CLL1) CAR T‐cells in refractory/relapsed acute myeloid leukemia (R/R‐AML) have been occasionally reported, the influence of co‐stimulatory domain CAR T‐cells is not investigated so far. Method Seven R/R‐AML children treated with anti‐CLL1 CAR T‐cells were enrolled onto this preliminary comparison study. Among these seven patients, four received CD28/CD27‐based CAR T‐cells therapy, and three received 4‐1BB‐based CAR T‐cells therapy. Result The overall response rates were 75% and 66.7% in CD28/CD27 and 4‐1BB group respectively. All patients experienced grade 1 to 2 cytokine release syndrome, with only one patient experiencing grade 2 immune effector cell‐associated neurotoxicity syndrome. The maximum CAR T‐cells durations were 156 and 274 days for CD28/CD27 group and 4‐1BB group respectively. The 1‐yr overall survival rate was 57.1%. Conclusions A preliminary similar efficacy/safety index was observed in anti‐CLL1‐based CAR T‐cells with 4‐1BB or CD28/CD27 co‐stimulatory elements in treating pediatric R/R‐AML. This preliminary report demonstrates that CD28/CD27‐ and 4‐1‐BB‐equipped CAR T‐cells have comparable effectiveness and safety indices in treating children with relapsed/refractoryacute myeloid leukemia.