演題詳細

一般口演 / Oral Session

一般口演 106 (Oral Session 106) :細胞・遺伝子治療:基礎

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日程
2013年10月13日(日)
時間
16:00 - 17:00
会場
第13会場 / Room No.13 (札幌市教育文化会館 3F 研修室301)
座長・司会
平家 勇司 (Yuji Heike):1
1:国立がん研究センター早期・探索臨床研究センター 免疫療法開発分野
 
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Novel strategy to treat GVHD with allele-specific anti-HLA killing antibody

演題番号 : OS-3-179

中内 祐介 (Yusuke Nakauchi):1、山崎 聡 (Satoshi Yamazaki):1、Stephanie Napier:2、渡辺 信和 (Nobukazu Watanabe):2、中内 啓光 (Hiromitsu Nakauchi):1

1:Div. Stem Cell Therapy, Inst. Med., Tokyo Univ., Japan、2:Lab. Diagnostic Medicine, Inst. Med., Tokyo Univ., Japan

 

Graft-versus-host disease (GVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation (HSCT) and can be lethal when current therapies fail.We have been generating various allele-specific anti-HLA monoclonal antibodies (ASHmAbs). We focused on the killing activity of these ASHmAbs, which recognize HLA alleles specifically and damage the cells. Our goal is to demonstrate the effectiveness of this Killing ASHmAb as a GVHD treatment.We transplanted HLA-A2+ or HLA-A2- peripheral blood mononuclear cells (PBMCs) from healthy donors into non-irradiated immunodeficient mice and generated a xenogeneic GVHD mouse model followed by administration of Killing ASHmAb to each mouse. A2+ mice all survived for more than 2 months, but A2- mice died off in less than 1.5 months. Flow cytometric analysis of mice PBMCs showed a decrease in A2+ human PBMCs. These results revealed that Killing ASHmAb damage the cells allele-specifically and improve the survival rate of GVHD mice. At the same time, an experiment comparing anti-thymocyte globulin showed that Killing ASHmAb can be an alternate drug as a GVHD treatment. We also generated humanized mice and administered Killing ASHmAb to each mouse. Most A2+ PBMCs disappeared although hematopoietic stem and progenitor cells in bone marrow were mildly damaged.We verified experimentally that Killing ASHmAb can quickly and selectively damage the target cells and treat GVHD mice. Because HLA-mismatched HSCTs are performed worldwide, Killing ASHmAb is a promising therapy to treat GVHD in a clinical setting.

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