Immune responses to intramuscular administration of alipogene tiparvovec (AAV1-LPL(S447X)) in a phase II clinical trial of lipoprotein lipase deficiency gene therapy.

ABSTRACT: Cellular immune responses to adeno-associated viral (AAV) vectors used for gene therapy have been linked to attenuated transgene expression and loss of efficacy. The impact of such cellular immune responses on the clinical efficacy of alipogene tiparvovec (Glybera; AAV1-LPL(S447X); uniQure), a gene therapy consisting of intramuscular administration of a recombinant AAV1 mediating muscle-directed expression of lipoprotein lipase (LPL), was investigated. Five subjects with LPL deficiency (LPLD) were administered intramuscularly with a dose of 1 × 10(12) gc/kg alipogene tiparvovec. All subjects were treated with immune suppression starting shortly before administration of alipogene tiparvovec and maintained until 12 weeks after administration. Systemic antibody and T cell responses against AA

SUBMITTER: Ferreira V 

PROVIDER: S-EPMC3955976 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature