小柯机器人

法国巴黎中心医院M. Cavazzana、英国大奥蒙德街医院A. J. Thrasher等研究人员合作完成慢病毒造血干细胞/祖细胞基因治疗威斯考特-阿尔德里奇综合征的长期安全性和疗效评估。该项研究成果于2022年1月24日在线发表在《自然—医学》杂志上。

研究人员为8名接受了I/II期基于慢病毒载体的基因治疗试验（NCT01347346和NCT01347242）的威斯卡特-阿德里奇综合征（WAS）患者提供了全面的长期随访结果（中位随访，7.6年）（I/II期试验编号：NCT02333760），重点关注血小板减少症和自身免疫力。长期研究的主要结果是通过评估严重不良事件的发生率和类型以及临床状态和生物参数，包括基因治疗后3年至15年不同细胞亚群中的慢病毒基因组整合位点，从而确定临床和生物安全性、有效性和耐受性。次要结果包括监测对额外治疗的需求和T细胞类群多样性。中期分析显示，鉴于基因校正的细胞稳定地移植，并且没有发生严重的治疗相关的不良事件，该研究符合测试的主要结果标准。

总体而言，严重的感染和湿疹得到了解决。自身免疫性疾病和出血发作明显减少，尽管只是部分纠正了血小板区间。这些结果表明，慢病毒基因疗法为WAS患者提供了持续的临床益处。

据介绍，缺乏人类白细胞抗原匹配供体的WAS患者可通过提供基因校正的自体造血干细胞/祖细胞从基因治疗中获益。

附：英文原文

Title: Long-term safety and efficacy of lentiviral hematopoietic stem/progenitor cell gene therapy for Wiskott–Aldrich syndrome

Author: Magnani, A., Semeraro, M., Adam, F., Booth, C., Dupr, L., Morris, E. C., Gabrion, A., Roudaut, C., Borgel, D., Toubert, A., Clave, E., Abdo, C., Gorochov, G., Petermann, R., Guiot, M., Miyara, M., Moshous, D., Magrin, E., Denis, A., Suarez, F., Lagresle, C., Roche, A. M., Everett, J., Trinquand, A., Guisset, M., Bayford, J. Xu, Hacein-Bey-Abina, S., Kauskot, A., Elfeky, R., Rivat, C., Abbas, S., Gaspar, H. B., Macintyre, E., Picard, C., Bushman, F. D., Galy, A., Fischer, A., Six, E., Thrasher, A. J., Cavazzana, M.

Issue&Volume: 2022-01-24

Abstract: Patients with Wiskott–Aldrich syndrome (WAS) lacking a human leukocyte antigen-matched donor may benefit from gene therapy through the provision of gene-corrected, autologous hematopoietic stem/progenitor cells. Here, we present comprehensive, long-term follow-up results (median follow-up, 7.6years) (phase I/II trial no. NCT02333760) for eight patients with WAS having undergone phase I/II lentiviral vector-based gene therapy trials (nos. NCT01347346 and NCT01347242), with a focus on thrombocytopenia and autoimmunity. Primary outcomes of the long-term study were to establish clinical and biological safety, efficacy and tolerability by evaluating the incidence and type of serious adverse events and clinical status and biological parameters including lentiviral genomic integration sites in different cell subpopulations from 3years to 15years after gene therapy. Secondary outcomes included monitoring the need for additional treatment and Tcell repertoire diversity. An interim analysis shows that the study meets the primary outcome criteria tested given that the gene-corrected cells engrafted stably, and no serious treatment-associated adverse events occurred. Overall, severe infections and eczema resolved. Autoimmune disorders and bleeding episodes were significantly less frequent, despite only partial correction of the platelet compartment. The results suggest that lentiviral gene therapy provides sustained clinical benefits for patients with WAS.

DOI: 10.1038/s41591-021-01641-x

Source: https://www.nature.com/articles/s41591-021-01641-x

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
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投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex