Development of next-generation antibody therapeutics by improving effector functions

Nakamura Kazuyasu, Sugimoto Yoshiyuki, Machino Yusuke, Natsume Akito, Sato Mitsuo

doi:10.2745/dds.26.611

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プロテインエンジニアリングを利用した次世代バイオ創薬　　エフェクター機能の増強による次世代抗体医薬の開発
エフェクター機能の増強による次世代抗体医薬の開発
エフェクターキノウノゾウキョウニヨルジセダイコウタイイヤクノカイハツ

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Abstract

To improve clinical efficacy of antibody therapeutics in humans, effector functions have been subjects of focus, especially antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Extensive efforts have been made to enhance these effector functions of antibodies, and successful approaches have been reported, wherein the binding activity of antibodies to FcγRIIIa or C1q is increased by introducing amino acid mutations into heavy chain constant regions or through glyco-modification of Fc-linked oligosaccharides. In addition, one of the next approaches to optimizing therapeutic antibodies would be to combine multiple enhancing modifications into a single antibody platform to overcome the diverse mechanisms of clinical resistance of tumor cells. For this aim, we have recently developed a successful combination composed of ADCC-enhancing modification by the fucose depletion from Fc-linked oligosaccharides and CDC-enhancing modification by IgG1 and IgG3 isotype shuffling in heavy chains, which could be of great value for the development of next-generation antibody therapeutics.

Journal

Drug Delivery System

Drug Delivery System 26 (6), 611-621, 2011

THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM

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