Modified lentiviral globin gene therapy for pediatric ß0/ß0 transfusion-dependent ß-thalassemia: A single-center, single-arm pilot trial.
Cell Stem Cell
; 31(7): 961-973.e8, 2024 Jul 05.
Article
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| MEDLINE
| ID: mdl-38759653
ABSTRACT
ß0/ß0 thalassemia is the most severe type of transfusion-dependent ß-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 ß-globin expression-optimized and insulator-engineered lentivirus-modified cell product (BD211) in ß0/ß0 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 ß-thalassemia.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Terapia Genética
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Talasemia beta
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Lentivirus
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Globinas beta
Límite:
Child
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Child, preschool
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Female
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Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article