次世代抗体医薬としてのポテリジェント抗体(誌上シンポジウム)
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概要
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Antibody-dependent cellular cytotoxicity (ADCC), a lytic attack on antibody-targeted cells, is triggered upon binding of lymphocyte receptors (FcγRs) to the antibody constant region. ADCC is considered to be a major therapeutic function of antibodies. ADCC requires the presence of oligosaccharides in the Fc region and is sensitive to change in the oligosaccharide structure. We have demonstrated that fucose is the most critical IgG1 oligosaccharide component, and the removal of fucose from IgG1 oligosaccharides results in a very significant enhancement of ADCC and anti-tumor activity in vivo. Many therapeutic antibodies approved or clinical development are produced using Chinese hamster ovary (CHO) cells that express high level of α1, 6-fucosyltransferase and consequently produce highly fucosylated antibodies. We have established the fucosyltransferase knockout CHO cells which could stably produce non-fucosylated antibodies, designated as Potelligent antibodies. Potelligent antibodies show potent ADCC upon target cells through the effective and antigen-specific activation of NK cells due to augmented binding to FcγRIIIa. Moreover, Potelligent antibodies can evade the inhibitory effect of plasma IgG on ADCC through its high FcγRIIIa binding. Thus, the application of Potelligent antibodies is expected to be a promising approach as next-generation therapeutic antibodies with improved efficacy, even when administered at low doses in humans in vivo.
- 2009-01-01
著者
関連論文
- 医療用抗体のADCC活性増強技術(ポテリジェント技術)について
- 次世代抗体医薬としてのポテリジェント抗体(誌上シンポジウム)
- 第4回 法人シンポジウム (第49回日本臨床化学会年次学術集会) : 抗体医薬と検査薬の今, そしてこれから