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 (CRS) was 95.2% (n = 20), with severe CRS occurring in 52.4% (n = 11) of the patients. Six patients (28.6%) developed neurotoxicity of any grade. GC007F demonstrated superior expansion capacity and a less exhausted phenotype as compared to (C-CAR-T) cells. Moreover, this first-in-human clinical study showed that the novel, next-day manufacturing FasTCAR-T cells was feasible with a manageable toxicity profile in patients with R/R B-ALL.

嵌合抗原受体工程 T (CAR-T) 细胞在复发/难治性 B 细胞急性淋巴细胞白血病 (R/R B-ALL) 患者中显示出良好的疗效。然而，挑战仍然存在，包括需要克服的漫长的制造过程。我们展示了第二天生产的靶向 CD19 的 CAR-T 细胞产品 GC007F（FasTCAR-T 细胞），并用于 R/R B-ALL 患者。共有 21 名 14 岁以上的 CD19 ^+患者对 R/R B-ALL 进行筛选、登记并以三种不同剂量水平的单次输注 GC007F CAR-T 进行输注。该研究的主要目的是评估安全性，次要目标包括 GC007F 细胞在 R/R B-ALL 患者中的药代动力学和初步疗效。我们能够在临床前研究中证明 GC007F 细胞比传统的 CAR-T (C-CAR-T) 细胞表现出更好的增殖和肿瘤杀伤能力。在这项由研究者发起的研究中，所有 18 名疗效可评估的患者在第 28 天达到完全缓解 (CR) (18/18, 100.00%)，其中 17 名患者 (94.4%) 达到完全缓解 (MRD) 阴性. 15 名 (83.3%) 在 3 个月评估时保持无病，14 名患者 (77.8%) 在第 3 个月保持 MRD 阴性。在所有 21 名入组患者中，CAR-T细胞的中位峰在第10天，中位峰拷贝数为104899.5/µg DNA，中位持续期为56天（范围：7-327天）。细胞因子释放综合征（CRS）的发生率为95.2%（n  = 20)，52.4% ( n  = 11) 的患者发生严重 CRS。6 名患者 (28.6%) 出现任何级别的神经毒性。与 (C-CAR-T) 细胞相比，GC007F 表现出卓越的扩增能力和较少耗尽的表型。此外，这项首次人体临床研究表明，新型、次日制造的 FasTCAR-T 细胞在 R/R B-ALL 患者中具有可控的毒性特征是可行的。