Modified lentiviral globin gene therapy for pediatric β 0 /β 0 transfusion-dependent β-thalassemia: A single-center, single-arm pilot trial.

Autor:	Li S; 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Kunming, Yunnan 650100, China., Ling S; Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China; BDgene Therapeutics, Shanghai 200240, China., Wang D; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China., Wang X; BDgene Therapeutics, Shanghai 200240, China., Hao F; BDgene Therapeutics, Shanghai 200240, China., Yin L; Sequanta Technologies, Shanghai 200131, China., Yuan Z; 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Kunming, Yunnan 650100, China., Liu L; 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Kunming, Yunnan 650100, China., Zhang L; BDgene Therapeutics, Shanghai 200240, China., Li Y; 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Kunming, Yunnan 650100, China., Chen Y; 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Kunming, Yunnan 650100, China., Luo L; 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Kunming, Yunnan 650100, China., Dai Y; 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Kunming, Yunnan 650100, China., Zhang L; 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Kunming, Yunnan 650100, China., Chen L; 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Kunming, Yunnan 650100, China., Deng D; Sequanta Technologies, Shanghai 200131, China., Tang W; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China., Zhang S; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China., Wang S; 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Kunming, Yunnan 650100, China. Electronic address: sanbin1011@163.com., Cai Y; Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: yujia.cai@sjtu.edu.cn.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2024 Jul 05; Vol. 31 (7), pp. 961-973.e8. Date of Electronic Publication: 2024 May 16.
DOI:	10.1016/j.stem.2024.04.021
Abstrakt:	β 0 /β 0 thalassemia is the most severe type of transfusion-dependent β-thalassemia (TDT) and is still a challenge facing lentiviral gene therapy. Here, we report the interim analysis of a single-center, single-arm pilot trial (NCT05015920) evaluating the safety and efficacy of a β-globin expression-optimized and insulator-engineered lentivirus-modified cell product (BD211) in β 0 /β 0 TDT. Two female children were enrolled, infused with BD211, and followed up for an average of 25.5 months. Engraftment of genetically modified hematopoietic stem and progenitor cells was successful and sustained in both patients. No unexpected safety issues occurred during conditioning or after infusion. Both patients achieved transfusion independence for over 22 months. The treatment extended the lifespan of red blood cells by over 42 days. Single-cell DNA/RNA-sequencing analysis of the dynamic changes of gene-modified cells, transgene expression, and oncogene activation showed no notable adverse effects. Optimized lentiviral gene therapy may safely and effectively treat all β-thalassemia. Competing Interests: Declaration of interests Y.C. is a co-founder and advisor of BDgene Therapeutics. S. Ling and X.W. filed two patents related to this work (“Lentiviral vector applicable to gene therapy of thalassemia and sickle anemia,” ZL201910824134.8, September 2, 2019, China; and “Lentiviral vector applicable to gene therapy of thalassemia and sickle anemia,” ZL202210013838.9, January 6, 2022, China). (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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