Genmab´s HexaBody® technology
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The HexaBody
technology is Genmab's proprietary antibody platform which allows for the creation of potent therapeutics by inducing antibody hexamer formation after target binding at the cell surfaceThe HexaBody technology builds on natural antibody biology and enhances the assembly of antibody hexamers (clusters of six) after target binding at the cell surface. This results in enhancement of immune effector functions including complement-mediated killing (complement-dependent cytotoxicity (CDC)). The HexaBody technology can transform antibodies with limited or absent CDC into potent, cytotoxic antibodies.
The HexaBody
technology builds on novel insights in the natural biology of antibodiesAntibodies play an important role in the activation of the complement system, a part of the innate immune system that is instrumental in the clearance of bacteria and viruses from the body. Antibodies can also be employed in therapy of detrimental diseases such as cancer. The importance of complement in antibody-mediated immunity and their therapeutic efficacy has been known for decades, yet only recently molecular insight was given into the interaction between IgG antibodies and complement.
Upon binding to their target molecules on a cell, antibodies were found to group together in rings of six:hexamers. This process is driven by non-covalent interactions between the Fc domains of adjacent antibodies. The formation of hexamers was found critical for optimal binding of the first component of the complement cascade, C1, which was evaluated by different exploratory techniques. Once this first component is bound, the complement cascade is triggered, eventually leading to formation of a membrane attack complex. This complex forms a hole in the cell membrane, and the cell dies.
By engineering the Fc domains of the antibodies, the hexamer formation may be increased whereby the efficacy of complement-dependent cytotoxicity (CDC) of target cells can be enhanced. This novel insight forms the basis of the HexaBody technology.
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Current progress in innovative engineered antibodies:
https://link.springer.com/article/10.1007/s13238-017-0457-8
Complement alone drives efficacy of a chimeric antigonococcal monoclonal antibody:
Complement alone drives efficacy of a chimeric antigonococcal monoclonal antibody
A chimeric antibody that contains a "complement-enhancing" mutation in Fc (so-called HexaBody technology) shows increased bactericidal activity compared to antibody bearing wild-type Fc and may represent a promising immunotherapeutic approach against multidrug-resistant gonorrhea.
(journals.plos.org)
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