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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 surface

The 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.


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The HexaBody technology is built on novel insight in the natural biology of antibodies. (1) The formation of antibody hexamers was found critical for optimal binding of the first component of the complement cascade, C1. (2) This concept of targeted assembly of antibodies into hexamers at the cell surface can be utilized to develop potentiated antibody therapeutics. (3) The HexaBody platform: antibody molecules with a single point mutation to enhance hexamerization upon cellular target binding, thereby strengthening the antibody’s potency.


The HexaBody platform creates opportunities to potentiate the intrinsic killing ability of therapeutic antibodies

  • Applicable to a wide range of antibodies directed to different targets
  • Broad potential for new or improved treatments for a variety of indications

The HexaBody technology can be combined with Genmab's DuoBody platform as well as with other antibody technologies. 

 

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The HexaBody® technology builds on novel insights in the natural biology of antibodies

Antibodies 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.

hexamerization

IgG bound to cell surface antigens (1) associates into hexameric platforms (2). This forms the optimal structure for binding of the first component of the complement system, C1 (3).

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