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Drug platforms

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 Genmab A/S' 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).

SciBX 7(13); doi:10.1038/scibx.2014.385
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