Assessment of Immune Responses Against AAV Encoded Transgene Products

This review article examines the immune responses associated with adeno-associated virus (AAV) encoded transgene products (TP). It discusses the increasing number of clinical investigations and applications of AAV-based gene therapies, focusing on how anti-AAV and anti-TP immune responses can impact the safety and efficacy of these treatments. The manuscript details the development of anti-TP antibodies and cytotoxic cellular responses, which may lead to the clearance of TPs and affect treatment durability. It outlines various immunogenicity risk factors that should be considered when evaluating the impact of anti-TP responses, including the importance of assessing these immune responses in clinical and non-clinical studies. The authors propose a structured approach for assessing anti-TP immunogenicity based on the nature of the TP and other risk factors. The article aims to provide guidance for industry sponsors, academic laboratories, and regulatory agencies involved in AAV-based therapies, promoting a consistent methodology for evaluating immune responses.