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科学家完成慢病毒基因疗法治疗β-血红蛋白病长期效果的临床试验
2022-01-30 23:13
来源：小柯机器人

法国巴黎大学Marina Cavazzana、Philippe Leboulch等研究人员合作完成慢病毒基因疗法治疗β-血红蛋白病长期效果的临床试验。相关论文于2022年1月24日在线发表在《自然—医学》杂志上。

HGB-205试验（NCT02151526）旨在评估自体CD34+细胞经慢病毒载体BB305体外转导的基因疗法，该载体编码在红细胞系中表达的抗镰状βA-T87Q球蛋白。HGB-205是一项1/2期、开放标签、单臂、非随机的干预性研究，在单一中心进行为期2年的研究，随后在长期随访研究LTF-303（NCT02633943）和LTF-307（NCT04628585）中分别观察输血依赖性β-地中海贫血（TDT）和镰状细胞病（SCD）。纳入和排除标准与异体移植相似，但仅限于缺乏基因相同、组织相容的供体的患者。四名TDT患者和三名SCD患者，年龄在13-21岁之间，在4.6-7.9年前接受了busulfan myeloablation治疗，中位随访时间为4.5年。关键的主要终点包括死亡率、移植率、复制能力强的慢病毒和克隆优势。没有观察到与药物产品有关的不良事件。在三名SCD患者中，有两名患者的临床缓解和疾病的生物标志得到了持续的补救，第三名患者的输血频率也有所降低。患有TDT的患者都没有输血，红细胞生成障碍和铁过载得到改善。
 
据悉，SCD和TDT是全世界最流行的单基因疾病。
 
附：英文原文
 
Title: Long-term outcomes of lentiviral gene therapy for the β-hemoglobinopathies: the HGB-205 trial

Author: Magrin, Elisa, Semeraro, Michaela, Hebert, Nicolas, Joseph, Laure, Magnani, Alessandra, Chalumeau, Anne, Gabrion, Aurlie, Roudaut, Ccile, Marouene, Jouda, Lefrere, Francois, Diana, Jean-Sebastien, Denis, Adeline, Neven, Bndicte, Funck-Brentano, Isabelle, Negre, Olivier, Renolleau, Sylvain, Brousse, Valentine, Kiger, Laurent, Touzot, Fabien, Poirot, Catherine, Bourget, Philippe, El Nemer, Wassim, Blanche, Stphane, Trluyer, Jean-Marc, Asmal, Mohammed, Walls, Courtney, Beuzard, Yves, Schmidt, Manfred, Hacein-Bey-Abina, Salima, Asnafi, Vahid, Guichard, Isabelle, Poire, Maryline, Monpoux, Fabrice, Touraine, Philippe, Brouzes, Chantal, de Montalembert, Mariane, Payen, Emmanuel, Six, Emmanuelle, Ribeil, Jean-Antoine, Miccio, Annarita, Bartolucci, Pablo, Leboulch, Philippe, Cavazzana, Marina

Issue&Volume: 2022-01-24

Abstract: Sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT) are the most prevalent monogenic disorders worldwide. Trial HGB-205 (NCT02151526) aimed at evaluating gene therapy by autologous CD34+ cells transduced ex vivo with lentiviral vector BB305 that encodes the anti-sickling βA-T87Q-globin expressed in the erythroid lineage. HGB-205 is a phase 1/2, open-label, single-arm, non-randomized interventional study of 2-year duration at a single center, followed by observation in long-term follow-up studies LTF-303 (NCT02633943) and LTF-307 (NCT04628585) for TDT and SCD, respectively. Inclusion and exclusion criteria were similar to those for allogeneic transplantation but restricted to patients lacking geno-identical, histocompatible donors. Four patients with TDT and three patients with SCD, ages 13–21 years, were treated after busulfan myeloablation 4.6–7.9 years ago, with a median follow-up of 4.5 years. Key primary endpoints included mortality, engraftment, replication-competent lentivirus and clonal dominance. No adverse events related to the drug product were observed. Clinical remission and remediation of biological hallmarks of the disease have been sustained in two of the three patients with SCD, and frequency of transfusions was reduced in the third. The patients with TDT are all transfusion free with improvement of dyserythropoiesis and iron overload.

DOI: 10.1038/s41591-021-01650-w

Source: https://www.nature.com/articles/s41591-021-01650-w

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
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex


本期文章：《自然—医学》：Online/在线发表

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