神母细胞瘤患者接受靶向GD2的嵌合抗原受体T细胞(CAR-T)治疗的长期疗效。

Long-term outcomes of GD2-directed CAR-T cell therapy in patients with neuroblastoma.

作者信息

Li Che-Hsing, Sharma Sandhya, Heczey Andras A, Woods Mae L, Steffin David H M, Louis Chrystal U, Grilley Bambi J, Thakkar Sachin G, Wu Mengfen, Wang Tao, Rooney Cliona M, Brenner Malcolm K, Heslop Helen E

机构信息

Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA.

Department of Pediatrics, Center for Advanced Innate Cell Therapy, Baylor College of Medicine, Houston, TX, USA.

出版信息

Nat Med. 2025 Apr;31(4):1125-1129. doi: 10.1038/s41591-025-03513-0. Epub 2025 Feb 17.

Abstract

In a phase 1 clinical trial open to accrual from 2004 to 2009, we treated children with neuroblastoma with Epstein-Barr virus (EBV)-specific T lymphocytes and CD3-activated T cells-each expressing chimeric antigen receptors (CARs) targeting GD2 but without an embedded co-stimulatory sequence (first-generation CARs). These CARs incorporated barcoded sequences to track each infused population. We previously reported outcomes up to 5 years and now report long-term outcomes up to 18 years. Of 11 patients with active disease at infusion, three achieved a complete response that was sustained in two patients, one for 8 years until lost to follow-up and one for more than 18 years. Of eight patients with no evidence of disease at the time of CAR-T administration, five are disease free at their last follow-up between 10 years and 15 years after infusion. Intermittent low levels of transgene were detected during the follow-up period with significantly greater persistence in those who were long-term survivors. Despite using first-generation vectors that are no longer employed because of the lack of co-stimulatory domains, patients with relapsed/refractory neuroblastoma achieved long-term disease control after receiving GD2 CAR-T cell therapy, including one patient now in remission of relapsed disease for more than 18 years.ClinicalTrials.gov identifier: NCT00085930 .

摘要

在一项于2004年至2009年期间开放入组的1期临床试验中,我们用靶向GD2的嵌合抗原受体(CAR)(第一代CAR,无嵌入共刺激序列)修饰的爱泼斯坦-巴尔病毒(EBV)特异性T淋巴细胞和CD3激活的T细胞治疗神经母细胞瘤患儿。这些CAR整合了条形码序列以追踪每个输注群体。我们之前报告了长达5年的结果,现在报告长达18年的长期结果。在输注时患有活动性疾病的11例患者中,3例实现了完全缓解,其中2例缓解持续,1例持续8年直至失访,另1例持续超过18年。在接受CAR-T治疗时无疾病证据的8例患者中,5例在输注后10年至15年的最后一次随访时无疾病。随访期间检测到间歇性低水平转基因,长期存活者中其持续性显著更高。尽管使用了因缺乏共刺激域而不再使用的第一代载体,但复发/难治性神经母细胞瘤患者在接受GD2 CAR-T细胞治疗后实现了长期疾病控制,包括1例目前复发疾病缓解超过18年的患者。临床试验注册号:NCT00085930。

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