TY - GEN
T1 - Strategy for a multicenter phase i clinical trial to evaluate globin gene transfer in β-thalassemia
AU - Sadelain, Michel
AU - Rivière, Isabelle
AU - Wang, Xiuyan
AU - Boulad, Farid
AU - Prockop, Susan
AU - Giardina, Patricia
AU - Maggio, Aurelio
AU - Galanello, Renzo
AU - Locatelli, Franco
AU - Yannaki, Evangelia
PY - 2010/8
Y1 - 2010/8
N2 - Globin gene transfer in autologous hematopoietic stem cells offers a potentially curative treatment option for patients suffering from β-thalassemia major who lack an HLA-matched hematopoietic stem cell donor. Based on extensive preclinical investigation, we are initiating a phase I clinical trial using G-CSF mobilized, autologous CD34+ cells transduced with a vector similar to the original TNS9 vector. Our first mobilizations in adult β-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.
AB - Globin gene transfer in autologous hematopoietic stem cells offers a potentially curative treatment option for patients suffering from β-thalassemia major who lack an HLA-matched hematopoietic stem cell donor. Based on extensive preclinical investigation, we are initiating a phase I clinical trial using G-CSF mobilized, autologous CD34+ cells transduced with a vector similar to the original TNS9 vector. Our first mobilizations in adult β-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.
KW - cell therapy
KW - globin gene regulation
KW - lentiviral vector
KW - non-myeloablative conditioning
KW - stem cell engineering
UR - http://www.scopus.com/inward/record.url?scp=77955904018&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955904018&partnerID=8YFLogxK
U2 - 10.1111/j.1749-6632.2010.05597.x
DO - 10.1111/j.1749-6632.2010.05597.x
M3 - Conference contribution
C2 - 20712772
AN - SCOPUS:77955904018
SN - 9781573317825
VL - 1202
T3 - Annals of the New York Academy of Sciences
SP - 52
EP - 58
BT - Annals of the New York Academy of Sciences
ER -