Thursday, January 23, 2014
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Asymmetrical Fc engineering
to enhance antibody-dependent cellular cytotoxicity (ADCC)
Antibodies engineered to
asymmetrically interact with Fc g-receptor IIIa (CD16a;
FcgRIIIa) could enhance ADCC. ADCC is
mediated through contact of antibody Fc chains with FCGR3A on NK cells upon
binding of tumor or viral antigen. In a heterodimeric Fc library, screening
of 9,000 individual antibody clones identified heterodimeric human IgG1
antibodies containing asymmetrical Fc mutations that increased binding to
FCGR3A and ADCC activity compared with wild-type human IgG1. In multiple
mouse xenograft models of cancer, heterodimeric IgG1 variants decreased tumor
size compared with normal IgG1. Next steps include enhancing ADCC activities
of therapeutic antibodies that are based on Fc heterodimers such as
Published online Jan. 23, 2014
Patent application filed;
licensing status undisclosed
Liu, Z. et al. J. Biol.
published online Dec. 5, 2013;
Contact: Wei Yan, Amgen Inc., Seattle, Wash.
Contact: Zhi Liu, same affiliation as above
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