BioAnalytical Scientist Sangamo Therapeutics Richmond, California
Gene therapy using recombinant adeno-associated virus (rAAV) as the delivery vehicle poses many new challenges for assessing immunogenicity. While anti-AAV neutralizing antibody (NAb) assays are widely utilized to assess pre-existing immunity to AAV capsids for enrolling treatment-responsive patients, it is also necessary to assay for the presence of antibodies against the expressed transgene. Many gene therapy programs are targeting inherited metabolic deficiency diseases with patient populations that are already being treated with enzyme replacement therapies. These patients often develop high levels of persistent antibodies to the recombinant protein products, which may impact the efficacy of gene therapy. Current published enzymatic NAb methods have not addressed the need for: generating a suitable positive control, appropriately setting the cutoff point, overcoming and improving drug tolerance, and reducing assay variability. This presentation will address these unique challenges pertinent to the development of an enzymatic NAb assay against a transgene-encoded protein expressed from a liver-tropic rAAV, to potentially inform clinical enrollment.
describe the importance of transgene immunogenicity assays for determining potential efficacy of gene therapy
explain key concepts and strategies on how to develop a clinically relevant enzymatic neutralizing antibody assay
elaborate on the use of immunogenicity assays to screen patients for enrollment; as opposed to the typical utility of determining antibody incidence post treatment