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Potent anti‐leukemia activities of humanized CD19‐targeted Chimeric antigen receptor T (CAR‐T) cells in patients with relapsed/refractory acute lymphoblastic leukemia

2018; Wiley; Volume: 93; Issue: 7 Linguagem: Inglês

10.1002/ajh.25108

1096-8652

Jiang Cao, Gang Wang, Hai Cheng, Wei Chen, Kunming Qi, Wei Sang, Zhenyu Li, Ming Shi, Huizhong Li, Jianlin Qiao, Bin Pan, Jing Zhao, Qingyun Wu, Lingyu Zeng, Mingshan Niu, Guangjun Jing, Junnian Zheng, Kailin Xu,

Virus-based gene therapy research

Chimeric antigen receptor T (CAR-T) cell therapy has shown promising results for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). The immune response induced by murine single-chain variable fragment (scFv) of the CAR may limit CAR-T cell persistence and thus increases the risk of leukemia relapse. In this study, we developed a novel humanized scFv from the murine FMC63 antibody. A total of 18 R/R ALL patients with or without prior murine CD19 CAR-T therapy were treated with humanized CD19-targeted CAR-T cells (hCART19s). After lymphodepletion chemotherapy with cyclophosphamide and fludarabine, the patients received a single dose (1 × 106 /kg) of autologous hCART19s infusion. Among the 14 patients without previous CAR-T therapy, 13 (92.9%) achieved complete remission (CR) or CR with incomplete count recovery (CRi) on day 30, whereas 1 of the 3 patients who failed a second murine CAR-T infusion achieved CR after hCART19s infusion. At day 180, the overall and leukemia-free survival rates were 65.8% and 71.4%, respectively. The cumulative incidence of relapse was 22.6%, and the nonrelapse mortality rate was 7.1%. During treatment, 13 patients developed grade 1-2 cytokine release syndrome (CRS), 4 patients developed grade 3-5 CRS, and 1 patient experienced reversible neurotoxicity. These results indicated that hCART19s could induce remission in patients with R/R B-ALL, especially in patients who received a reinfusion of murine CAR-T.