Unraveling the Complex Story of Immune Responses to AAV Vectors Trial After Trial
In: ISSN: 1043-0342, 2017
Online
academicJournal
Zugriff:
International audience ; 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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Unraveling the Complex Story of Immune Responses to AAV Vectors Trial After Trial
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Autor/in / Beteiligte Person: | Vandamme, Céline ; Adjali, Oumeya ; Mingozzi, Federico ; Department of Clinical Microbiology Kuopio, Finland ; University of Eastern Finland-Institute of Clinical Medicine Kuopio, Finland ; Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques (Inserm UMR 1089) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE) ; Université de Nantes (UN)-Université de Nantes (UN) ; Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE) ; École Pratique des Hautes Études (EPHE) ; Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon ; Centre de recherche en Myologie – U974 SU-INSERM ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU) ; F.M.’s work was supported by Genethon. It was also supported by the European Union’s research and innovation program under Grant Agreement No. 667751 (MYOCURE to F.M.), the European Research Council Consolidator Grant under Grant Agreement No. 617432 (MoMAAV to F.M.), and the R-Rare2 consortium grant SMART-HaemoCare. O.A. and C.V. were supported by the Inserm, the French Ministry of Research, the F.R.M. (Fondation pour la Recherche Me´dicale), the University Hospital of Nantes, the Fondation pour la Thérapie Génique en Pays de Loire, the AFM-Téléthon (Association Française contre les Myopathies), the Région Pays de la Loire (IMBIO-DC consortium), and the IHU-CESTI, which is supported by the French National Research Agency (ANR) via the ‘‘Investment Into The Future’’ program ANR-10-IBHU-005. ; ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010) ; European Project: 667751,H2020,H2020-PHC-2015-two-stage,MYOCURE(2016) ; European Project: 617432,EC:FP7:ERC,ERC-2013-CoG,MOMAAV(2014) |
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Zeitschrift: | ISSN: 1043-0342, 2017 |
Veröffentlichung: | HAL CCSD ; Mary Ann Liebert, 2017 |
Medientyp: | academicJournal |
DOI: | 10.1089/hum.2017.150 |
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