학술논문
Changing the Natural History of Fanconi Anemia Complementation Group-A with Gene Therapy: Early Results of U.S. Phase I Study of Lentiviral-Mediated Ex-Vivo FANCAGene Insertion in Human Stem and Progenitor Cells
Document Type
Article
Author
Source
Blood; November 2019, Vol. 134 Issue: 1, Number 1 Supplement 1 p3350-3350, 1p
Subject
Language
ISSN
00064971; 15280020
Abstract
Background: Fanconi anemia (FA) is a rare genetic disorder characterized by defective cellular deoxyribonucleic acid (DNA) repair, associated with developmental abnormalities, progressive bone marrow failure (BMF), and a predisposition to hematologic malignancies and solid tumors. 80% of FA patients develop BMF. Although allogeneic hematopoietic stem cell transplant (allo-HSCT) is a curative treatment for BMF, its utilization and efficacy is limited by availability of suitable human leukocyte antigen (HLA)-matched donors, risk of graft-versus-host disease (GVHD) and transplant-related toxicities. Ex-vivoinsertion of a functional FANCAgene into autologous FA-A CD34+ enriched hematopoietic stem and progenitor cells (HSPCs) has been shown in preclinical studies to provide a survival advantage to the gene-modified stem cells, leading to correction of BMF. Feasibility of this approach was established in the FANCOLEN-1 clinical trial (Spain), although cell doses and transduction levels varied considerably. Modifications to the collection and manufacturing processes were made in the clinical studies to enhance the dose of transduced HSPCs, with the goal of preventing progression of BMF to obviate the need of an allo-HSCT.