A previously published clinical trial demonstrated the benefit of autologous CD34(+) cells transduced with a selfinactivating lentiviral vector (HPV569) containing an engineered b-globin gene (b(A- @entity68497 )-globin) in a subject with b @entity2395 major. This vector has been modified to increase transduction efficacy without compromising safety. In vitro analyses indicated that the changes resulted in both increased vector titers (3 to 4 fold) and increased transduction efficacy (2 to 3 fold). An in vivo study in which 58 b-thalassemic @entity19 were transplanted with vector- or mock-transduced syngenic bone marrow cells indicated sustained therapeutic efficacy. Secondary transplantations involving 108 recipients were performed to evaluate long-term safety. The six month study showed no hematological or biochemical @entity137 . Integration site (IS) profile revealed an oligo/polyclonal hematopoietic reconstitution in the primary transplants and reduced clonality in secondary transplants. @entity5 cells were detected in the secondary transplant @entity19 in all treatment groups (including the control group), without statistical differences in the @entity5 incidence. Immunohistochemistry and quantitative PCR demonstrated that @entity5 cells were not derived from transduced donor cells. This comprehensive efficacy and safety data provided the basis for initiating two clinical trials with this second generation vector (BB305) in Europe and in the USA in @entity1 with @entity2395 major and @entity3458 .

Preclinical Evaluation of Efficacy and Safety of an Improved Lentiviral Vector for the Treatment of @entity2395 and XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'Tumor'] @entity3458 :: ('MESH:D000755', 'Disease') :: ['sickle cell disease'] @entity68497 :: ('p|SUB|T|87|Q', 'ProteinMutation') :: ['T87Q'] @entity2395 :: ('MESH:D013789', 'Disease') :: ['b-thalassemia', 'thalassemia']
@entity3458 :: (MESH:D000755,Disease) :: ['Sickle Cell Disease']
