演題詳細

ポスター / Poster

ポスター 47 (Poster 47) :細胞療法

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日程
2013年10月11日(金)
時間
16:50 - 17:50
会場
ポスター会場 / Poster (ロイトン札幌 3F エメラルドABCD)
座長・司会
三浦 康生 (Yasuo Miura):1
1:京都大学医学部附属病院 輸血細胞治療部
 
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Precise evaluation of NAb against AAV vectors and approaches toward managing its inhibitory effect

演題番号 : PS-1-360

水上 浩明 (Hiroaki Mizukami):1、三室 淳 (Jun Mimuro):2、内堀 亮介 (Ryosuke Uchibori):1、塚原 智典 (Tomonori Tsukahara):1、卜部 匡司 (Masashi Urabe):1、久米 晃啓 (Akihiro Kume):1、坂田 飛鳥 (Asuka Sakata):2、大森 司 (Tsukasa Ohmori):2、窓岩 清治 (Seiji Madoiwa):2、坂田 洋一 (Yoichi Sakata):2、小澤 敬也 (Keiya Ozawa):1

1:Div. Genetic Therapeutics, Ctr Mol. Med., Jichi Med. Univ., Japan、2:Div. of Cell and Molecular Medicine, Jichi Med. Univ., Japan

 

Adeno-associated virus (AAV) vectors are suitable in gene therapy, especially for hemophilia. For the liver-mediated approach, IV injection of AAV8 vector is shown to be effective including humans. On the other hand, inhibitory actions of pre-existing neutralizing antibody (NAb) against vector capsid, even at marginal levels, are also demonstrated, suggesting the necessity of more sensitive assay for NAb detection. To solve this issue, we have improved the assay for NAb against AAV capsids. As a result, all of the 9 monkeys judged as NAb-negative by this method showed transgene expression at the expected levels. Remaining challenge is whether AAV-mediated gene therapy is available to NAb-positive subjects. For this purpose, we developed a methodology to inject saline before and after vector injection in order to avoid contact of vectors with neutralizing antibodies (saline flushing). Both direct injection and balloon catheter-guided injection of the AAV8 vector into the portal vein of 6 NAb-positive macaques using saline flushing method achieved transgene-derived FIX expression at the levels comparable to that of NAb-negative monkeys, suggesting clinical applicability. This study was performed in collaboration with Division of Medical Skill Training, Center for Development of Advanced Medical Technology, Jichi Medical University, Cardiology Division of Department of Medicine, Jichi Medical University, Tsukuba Primate Research Center, National Institute for Biomedical Innovation, and The Corporation for Production and Research of Laboratory Primates, Japan.

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