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，仍存在包括较长的制备过程在内的挑战需要克服。我们介绍了次日制备的靶向CD19的CAR-T细胞产品GC007F（FasTCAR-T细胞），并将其用于R/R B-ALL患者。共有21名14岁以上CD19阳性的R/R B-ALL患者经过筛选、入组，并接受了单次GC007F CAR-T细胞输注，分为三个不同剂量水平。研究的主要目的是评估安全性，次要目的包括GC007F细胞在R/R B-ALL患者中的药代动力学及初步疗效。临床前研究表明，GC007F细胞比传统CAR-T（C-CAR-T）细胞表现出更好的增殖和肿瘤杀伤能力。在这项研究者发起的研究中，所有18名可评估疗效的患者在第28天均达到完全缓解（CR）（18/18，100.00%），其中17名患者（94.4%）达到微小残留病（MRD）阴性的完全缓解。在3个月评估时，15名患者（83.3%）保持无病状态，14名患者（77.8%）在3个月时仍保持MRD阴性。在所有21名入组患者中，CAR-T细胞的中位峰值出现在第10天，中位峰值拷贝数为104899.5/微克DNA，中位持续时间为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），其中严重CRS发生率为52.4%（n=11）。6名患者（28.6%）出现了任何级别的神经毒性。与C-CAR-T细胞相比，GC007F表现出更优的扩增能力和较低的耗竭表型。此外，这项首次人体临床研究表明，新型的次日制备FasTCAR-T细胞在R/R B-ALL患者中具有可行性，且毒性可控。
Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia
肿瘤(癌症)患者之家