文章：

次日制备的抗CD19 CAR-T细胞疗法用于B细胞急性淋巴细胞白血病的首次人体临床研究

Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study

原文发布日期：2022-07-07

DOI: 10.1038/s41408-022-00694-6

类型: Article

开放获取: 是

英文摘要：

To improve clinical outcomes and shorten the vein-to-vein time of chimeric antigen receptor T (CAR-T) cells, we developed the FasT CAR-T (F-CAR-T) next-day manufacturing platform. We report the preclinical and first-in-human clinical studies evaluating the safety, feasibility, and preliminary efficacy of CD19 F-CAR-T in B-cell acute lymphoblastic leukemia (B-ALL). CD19 F-CAR-T cells demonstrated excellent proliferation with a younger cellular phenotype, less exhaustion, and more effective tumor elimination compared to conventional CAR-T cells in the preclinical study. In our phase I study (NCT03825718), F-CAR-T cells were successfully manufactured and infused in all of the 25 enrolled pediatric and adult patients with B-ALL. CD19 F-CAR-T safety profile was manageable with 24% grade 3 cytokine release syndrome (CRS) and 28% grade 3/4 neurotoxicity occurring predominantly in pediatric patients. On day 14, 23/25 patients achieved minimal residual disease (MRD)-negative complete remission (CR), and 20 subsequently underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 3 months post F-CAR-T therapy. Fifteen of 20 patients were disease-free with a median remission duration of 734 days. One patient relapsed and 4/20 died from transplant-related mortality. Of the three patients who did not undergo allo-HSCT, two remained in CR until 10 months post-F-CAR-T. Our data indicate that anti-CD19 FasT CAR-T shows promising early efficacy for B-ALL. Further evaluations in larger clinical studies are needed.
 

摘要翻译： 

为改善临床疗效并缩短嵌合抗原受体T细胞（CAR-T）的静脉至静脉时间，我们开发了次日制备的FasT CAR-T（F-CAR-T）生产平台。本文报告评估CD19 F-CAR-T治疗B细胞急性淋巴细胞白血病（B-ALL）的安全性、可行性和初步疗效的临床前及首次人体临床研究。临床前研究表明，与传统CAR-T细胞相比，CD19 F-CAR-T细胞表现出更优的增殖能力、更年轻的细胞表型、更低耗竭状态及更强的肿瘤清除效果。在Ⅰ期临床试验（NCT03825718）中，25例入组的儿童及成人B-ALL患者均成功完成F-CAR-T细胞制备与输注。CD19 F-CAR-T安全性可控，其中24%发生3级细胞因子释放综合征，28%出现3/4级神经毒性（主要集中于儿童患者）。第14天时，23/25例患者达到微小残留病阴性完全缓解，其中20例在F-CAR-T治疗后3个月内接受异基因造血干细胞移植。20例移植患者中15例维持无病状态（中位缓解期734天），1例复发，4例死于移植相关并发症。在未接受移植的3例患者中，2例在F-CAR-T治疗后10个月内持续保持完全缓解。本研究数据表明，抗CD19 FasT CAR-T对B-ALL具有显著的早期疗效，尚需更大规模的临床研究进一步验证。

原文链接：

Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study