Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia

作者：Cheng Zhang, Jiaping He, Li Liu, Jishi Wang, Sanbin Wang, Ligen Liu, Jian Ge, Lei Gao, Li Gao, Peiyan Kong, Yao Z. Liu, Jia Liu, Yu Han, Yongliang Zhang, Zhe Sun, Xun Ye, Wenjie Yin, Martina A. Sersch, Lianjun Shen, Wei William Cao, Xi Zhang · 发表于：Blood Cancer Journal · 年份：2022 · DOI：10.1038/s41408-022-00688-4 · 被引用次数：41 · 研究领域：CAR-T cell therapy research、Advancements in Semiconductor Devices and Circuit Design、Nanowire Synthesis and Applications

Abstract Chimeric antigen receptor-engineered T (CAR-T) cells have shown promising efficacy in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL). However, challenges remain including long manufacturing processes that need to be overcome. We presented the CD19-targeting CAR-T cell product GC007F manufactured next-day (FasTCAR-T cells) and administered to patients with R/R B-ALL. A total of 21 patients over 14 years of age with CD19+ R/R B-ALL were screened, enrolled and infused with a single infusion of GC007F CAR-T at three different dose levels. The primary objective of the study was to assess safety, secondary objectives included pharmacokinetics of GC007F cells in patients with R/R B-ALL and preliminary efficacy. We were able to demonstrate in preclinical studies that GC007F cells exhibited better proliferation and tumor killing than conventional CAR-T (C-CAR-T) cells. In this investigator-initiated study all 18 efficacy-evaluable patients achieved a complete remission (CR) (18/18, 100.00%) by day 28, with 17 of the patients (94.4%) achieving CR with minimal residual disease (MRD) negative. Fifteen (83.3%) remained disease free at the 3-month assessment, 14 patients (77.8%) maintaining MRD negative at month 3. Among all 21 enrolled patients, the median peak of CAR-T cell was on day 10, with a median peak copy number of 104899.5/µg DNA and a median persistence period of 56 days (range: 7–327 days). The incidence of cytokine release syndrome (...