人間総合科学研究科「医学セミナー」 演題: タンパク質工学を駆使した 次世代がん治療抗体の開発 演者: 浅野竜太郎 准教授 東京農工大学大学院 工学研究院生命機能科学部門 日付: 2016 年 12 月 2 日(金) 時間: 18:30 ~ 19:30 場所: 臨床講義室 C 本セミナーは主に英語で行われます。 要 旨 : To date, several types of recombinant antibody, e.g. fused with toxins, multivalent, and multispecific, have been designed in efforts to develop next-generation antibodies with higher function. Among recombinant antibodies, bispecific antibodies are one of attractive formats that can bind to two different targets. This bispecificity can be applied to cancer therapy by cross-linking between tumor cells and immune cells. We have focused on small bispecific antibodies because they are easy to be modified through genetic engineering, and found that a humanized small bispecific antibody, designated as Ex3, that targets epidermal growth factor receptor (EGFR) on tumor cells and CD3 on T-lymphocytes, had marked anticancer activity. Furthermore, the anticancer effect of Ex3 was enhanced by fusion with the human Fc region, multimerization, domain rearrangement, and affinity maturation; a combination of these modifications showed at least additive effects. Interestingly, merely rearranging the domain order of Ex3 induced substantial cytotoxic enhancements, enhanced degradation resistance, and prolonged in vivo half-life. More recently, we also constructed humanized anti-EGFR single-chain variable fragment (scFv) multimers by modifying the linker length and the domain order, and evaluated their ability to inhibit tumor growth. The anti-EGFR scFv multimers inhibited cancer growth in a multimerization-dependent manner, whereas the anti-EGFR scFv monomer showed no inhibitory effects. Here, I will present our efforts to develop functional recombinant antibodies as next-generation cancer therapeutic reagents using protein engineering. 連絡先: 医学医療系 細菌学 森川一也 (3928, 7882) <This seminar will be held in English.> Date: Dec. 2 (Fri) 2016 18:30-19:30 Venue: Clinical Lecture Room C Title: Development of next-generation cancer therapeutic antibodies by using protein engineering Speaker: Dr. Ryutaro Asano Department of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology Kazuya Morikawa, Department of Infection Biology (Bacteriology) [email protected] 029-853-7882
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