2026-04-20 カリフォルニア大学ロサンゼルス校（UCLA）
＜関連情報＞
- https://newsroom.ucla.edu/releases/gene-therapy-research-sickle-cell-disease-taught-ucla-scientists
- https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2026019869/567840/Clinical-Outcomes-of-Lentiviral-Vector-Gene
鎌状赤血球症に対するレンチウイルスベクター遺伝子治療の臨床成績 Clinical Outcomes of Lentiviral Vector Gene Therapy for Sickle Cell Disease
Chattip Prueksapraopong,Augustine Fernandes,Beatriz Campo Fernandez,Sohini Roy,Roger P Hollis,Bruck Habtemariam,Danilo Pellin,Giacomo Ceoldo,Tsai-Yu Lin,Thao Thi Dang,Kenneth Cornetta,Zulema Romero,Bruce R. Blazar,Ami J. Shah,Theodore B Moore,Mary Sehl,Gary J. Schiller,Donald B. Kohn
Blood Advances Published:April 20, 2026
DOI:https://doi.org/10.1182/bloodadvances.2026019869
Key Points
- Autologous lentiviral gene therapy for sickle cell disease is feasible and was not associated with vector-related serious adverse events
- Optimized stem cell collection, vectors design, transduction, and conditioning improved gene marking and therapeutic hemoglobin expression.
Sickle cell disease (SCD) is a monogenic disorder where autologous gene therapy may offer a safer curative alternative to allogeneic transplantation. We report outcomes from a Phase I/II study using the Lenti/G-βAS3-FB lentiviral vector, encoding an anti-sickling β-globin. This trial was registered at ClinicalTrials.gov (NCT02247843). This single-site study treated four adults with severe SCD. The first patient was treated using the original Lenti/βAS3-FB and initial protocol, which resulted in suboptimal clinical response. Subsequent protocol refinements included improved hematopoietic stem and progenitor cell (HSPC) collection using plerixafor-mobilized peripheral blood apheresis with pre-collection erythrocytapheresis, and use of an optimized lentiviral vector with a transduction enhancer. All patients received myeloablative busulfan conditioning followed by infusion of gene-modified autologous HSPCs. Primary endpoints were safety and feasibility; secondary endpoints included gene marking, therapeutic hemoglobin expression, and clinical outcomes. All patients achieved hematopoietic recovery without rescue transplantation. The first patient demonstrated low gene marking (peak vector copy number [VCN] 0.035) and undetectable HbAS3 expression, with minimal clinical benefit. In contrast, the three patients treated with the optimized protocol achieved higher and sustained gene marking (peak granulocyte VCNs ~0.5-2.0) and persistent HbAS3 expression. These patients experienced some reductions in vaso-occlusive crises and transfusion requirements, with two becoming transfusion-independent. No insertional oncogenesis was observed. This trial highlights the necessity of optimized vector design and transduction protocols to achieve durable gene expression. While this specific vector will not be pursued further, the study provides crucial insights into gene therapy protocol development.
