Potelligent antibodies as next generation therapeutic antibodies

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
Kenya Shitara

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...Continue Reading

References

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Citations

Nov 23, 2012·Biotechnology Progress·Seshu TummalaAnthony Rossomando
May 4, 2011·American Journal of Human Biology : the Official Journal of the Human Biology Council·Gillian H IceElizabeth Juma
May 30, 2012·Biotechnology Progress·P A Marichal-Gallardo, M M Alvarez
Apr 5, 2014·Journal of Molecular Recognition : JMR·Simon J MountfordMilton T W Hearn
Sep 10, 2015·The Cochrane Database of Systematic Reviews·Megan K YoungMieke L van Driel
Apr 13, 2018·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·Kenichiro TodorokiToshimasa Toyo'oka

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