Unraveling the Complex Story of Immune Responses to AAV Vectors Trial After Trial - Inserm - Institut national de la santé et de la recherche médicale
Journal Articles Human Gene Therapy Year : 2017

Unraveling the Complex Story of Immune Responses to AAV Vectors Trial After Trial

Abstract

Over the past decade, vectors derived from adeno-associated virus (AAV) have established themselves as apowerful tool for in vivo gene transfer, allowing long-lasting and safe transgene expression in a variety of humantissues. Nevertheless, clinical trials demonstrated how B and T cell immune responses directed against the AAVcapsid, likely arising after natural infection with wild-type AAV, might potentially impact gene transfer safetyand efficacy in patients. Seroprevalence studies have evidenced that most individuals carry anti-AAV neutralizingantibodies that can inhibit recombinant AAV transduction of target cells following in vivo administration ofvector particles. Likewise, liver- and muscle-directed clinical trials have shown that capsid-reactive memoryCD8+T cells could be reactivated and expanded upon presentation of capsid-derived antigens on transduced cells,potentially leading to loss of transgene expression and immune-mediated toxicities. In celebration of the 25thanniversary of the European Society of Gene and Cell Therapy, this review article summarizes progress madeduring the past decade in understanding and modulating AAV vector immunogenicity. While the knowledgegenerated has contributed to yield impressive clinical results, several important questions remain unanswered,making the study of immune responses to AAV a priority for the field of in vivo transfer.
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Dates and versions

inserm-01798967 , version 1 (24-05-2018)

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Céline Vandamme, Oumeya Adjali, Federico Mingozzi. Unraveling the Complex Story of Immune Responses to AAV Vectors Trial After Trial. Human Gene Therapy, 2017, 28 (11), pp.1061 - 1074. ⟨10.1089/hum.2017.150⟩. ⟨inserm-01798967⟩
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