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Evaluation of the humoral response to viral-based Gene Therapy Modalities using Total Antibody assays

Milton, Mark, Gorovits, Boris, Azedeh, Mitra, Buchlis, George, Harrisson, Travis, Havert, Mike, Jawa, Vibha, Long, Brian, McNally, Jim, Nelson, Robert, O'Dell, Mark, Richards, Karen, Vetterman, Christian and Wu, Bonnie (2021) Evaluation of the humoral response to viral-based Gene Therapy Modalities using Total Antibody assays. The AAPS journal, 23. p. 108. ISSN 1550-7416


The number of viral vector-based gene therapies (GTx) continues to grow with 2 products (Zolgensma® and Luxturna®) approved in the US as of March 2021. To date, one of the most commonly used vectors are adeno-associated virus (AAV) based. The pre-existing humoral immunity against AAV (anti-AAV antibodies) has been well described and is expected as a consequence of endogenous AAV infections. High prevalence of anti-AAV antibodies may present a barrier to successful AAV transduction and hence negatively impact clinical efficacy and may also result in Adverse Events (AEs) as a consequence of the formation of large immune complexes. Patients may be screened for the presence of anti-AAV antibodies, including neutralizing (NAb) and total binding antibodies (TAb) prior to treatment with the GTx. Recommendations for the development and validation of anti-AAV NAb detection methods has been presented elsewhere. This manuscript covers considerations related to anti-AAV TAb detecting protocols, including the benefits of the use of TAb methods, selection of assay controls and reagents, and parameters critical to monitoring assay performance. This manuscript was authored by a group of scientists involved in GTx development representing 11 companies. It is our intent to provide recommendations and guidance to industrial sponsors and academic laboratories working on viral vector based GTx modalities with the goal of achieving a more consistent approach to anti-AAV TAb assessment.

Item Type: Article
Keywords: Humoral Immune response; binding antibody; Gene Therapy; AAV
Date Deposited: 22 Feb 2022 00:45
Last Modified: 22 Feb 2022 00:45


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