期刊
HUMAN GENE THERAPY
卷 28, 期 11, 页码 1061-1074出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/hum.2017.150
关键词
AAV vectors; immune responses; T cells; antibody responses; gene therapy
资金
- Genethon
- European Union [667751]
- European Research Council [617432]
- R-Rare2 consortium grant SMART-HaemoCare
- Inserm
- French Ministry of Research
- F.R.M. (Fondation pour la Recherche Medicale)
- University Hospital of Nantes
- Fondation pour la Therapie Genique en Pays de Loire
- AFM-Telethon (Association Francaise contre les Myopathies)
- Region Pays de la Loire (IMBIO-DC consortium)
- IHU-CESTI - French National Research Agency (ANR) via the Investment Into The Future program [ANR-10-IBHU-005]
- European Research Council (ERC) [617432] Funding Source: European Research Council (ERC)
Over the past decade, vectors derived from adeno-associated virus (AAV) have established themselves as a powerful tool for in vivo gene transfer, allowing long-lasting and safe transgene expression in a variety of human tissues. Nevertheless, clinical trials demonstrated how B and T cell immune responses directed against the AAV capsid, likely arising after natural infection with wild-type AAV, might potentially impact gene transfer safety and efficacy in patients. Seroprevalence studies have evidenced that most individuals carry anti-AAV neutralizing antibodies that can inhibit recombinant AAV transduction of target cells following in vivo administration of vector particles. Likewise, liver- and muscle-directed clinical trials have shown that capsid-reactive memory CD8(+) 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 25th anniversary of the European Society of Gene and Cell Therapy, this review article summarizes progress made during the past decade in understanding and modulating AAV vector immunogenicity. While the knowledge generated 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据