[Potelligent antibodies as next generation therapeutic antibodies].

  • Kenya Shitara
  • Published 2009 in
    Yakugaku zasshi : Journal of the Pharmaceutical…

Abstract

Antibody-dependent cellular cytotoxicity (ADCC), a lytic attack on antibody-targeted cells, is triggered upon binding of lymphocyte receptors (FcgammaRs) 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 alpha1,6-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 FcgammaRIIIa. Moreover, Potelligent antibodies can evade the inhibitory effect of plasma IgG on ADCC through its high FcgammaRIIIa 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.

Statistics

020040060080020132014201520162017
Citations per Year

262 Citations

Semantic Scholar estimates that this publication has 262 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Shitara2009PotelligentAA, title={[Potelligent antibodies as next generation therapeutic antibodies].}, author={Kenya Shitara}, journal={Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan}, year={2009}, volume={129 1}, pages={3-9} }