Evaluation of Cellular Immune Response to Adeno-Associated Virus-Based Gene Therapy
- PMID: 37101079
- PMCID: PMC10132926
- DOI: 10.1208/s12248-023-00814-5
Evaluation of Cellular Immune Response to Adeno-Associated Virus-Based Gene Therapy
Abstract
The number of approved or investigational late phase viral vector gene therapies (GTx) has been rapidly growing. The adeno-associated virus vector (AAV) technology continues to be the most used GTx platform of choice. The presence of pre-existing anti-AAV immunity has been firmly established and is broadly viewed as a potential deterrent for successful AAV transduction with a possibility of negative impact on clinical efficacy and a connection to adverse events. Recommendations for the evaluation of humoral, including neutralizing and total antibody based, anti-AAV immune response have been presented elsewhere. This manuscript aims to cover considerations related to the assessment of anti-AAV cellular immune response, including review of correlations between humoral and cellular responses, potential value of cellular immunogenicity assessment, and commonly used analytical methodologies and parameters critical for monitoring assay performance. This manuscript was authored by a group of scientists involved in GTx development who represent several pharma and contract research organizations. It is our intent to provide recommendations and guidance to the industry sponsors, academic laboratories, and regulatory agencies working on AAV-based GTx viral vector modalities with the goal of achieving a more consistent approach to anti-AAV cellular immune response assessment.
Keywords: AAV; Adeno-associated virus; Cellular immune response; anti-AAV immunogenicity.
© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.
Conflict of interest statement
The authors are employed by and receive compensation from companies that are involved in development of gene therapy modality therapeutics and are listed on the title page of the manuscript. The authors have no other relevant affiliations or financial involvements with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
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