Thursday, April 3, 2014
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Hexamer-forming mAbs that
activate the complement system
mAbs engineered with
mutations that promote hexamer formation could help treat infections and
cancer by activating the complement system. The complement system is a part
of the innate immune system that helps to eliminate pathogens and tumor
cells. In cell culture, multiple IgGs engineered with an E345R mutation had
greater complement-dependent cytotoxicity than unmodified variants. In
vitro, IgGs with the E345R mutation were better than control IgGs at
forming hexameric structures that activated complement
component 1 q subcomponent (C1q)
after binding to their target antigen. Next steps include selecting
complement activation-enhancing mutations and specific mAb variants to use in
HexaBody platform for generating therapeutic antibodies.
Genmab uses its HexaBody platform to design mAbs that have an improved
ability to eliminate pathogens and tumor cells while retaining their regular
structure and specificity (see Complementing mAbs, page 7).
Published online April 3, 2014
Patent application filed;
available for licensing and partnering
Diebolder, C.A. et al.
Science; published online March 14, 2014;
Contact: Paul W.H.I. Parren, Genmab A/S, Utrecht, the Netherlands
Contact: Piet Gros, Utrecht University, Utrecht, the Netherlands
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