Journal
COOLEY'S ANEMIA: NINTH SYMPOSIUM
Volume 1202, Issue -, Pages 52-58Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1749-6632.2010.05597.x
Keywords
cell therapy; globin gene regulation; lentiviral vector; non-myeloablative conditioning; stem cell engineering
Categories
Funding
- Sloan-Kettering Institute
- Leonardo Giambronc Foundation
- National Heart, Lung, and Blood Institute
- Cooley's Anemia Foundation
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Globin gene transfer in autologous hematopoietic stem cells offers a potentially curative treatment option for patients suffering from beta-thalassemia major who lack an HLA-matched hematopoietic stem cell donor. Based on extensive preclinical investigation, we are initiating a phase 1 clinical trial using G-CSE mobilized, autologous CD34(+) cells transduced with a vector similar to the original TNS9 vector. Our first mobilizations in adult beta-thalassemic subjects have been well tolerated and yielded the required CD34(+) cell dose. To minimize toxicity to enrolled subjects, and in the absence of a demonstrated requirement for myeloablative conditioning, our trial will use a reduced intensity conditioning regimen. Because low vector titers may adversely affect efficacy and safety, we have focused on vector manufacturing processes. We are now in a position to transfer our globin lentiviral vectors in a clinically relevant dosage (averaging 0.8 vector copy per cell in bulk CD34(+) cells) and to supply clinical grade vector to collaborating centers in the U.S.A. and in Europe. We anticipate that the first U.S. trial of globin gene transfer will start in 2010.
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