Pioneering technologies that create novel antibody therapeutics to treat cancer and other serious diseases.
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Antibody Technology Platforms
HexElect®
HexElect® is a combination of two HexaBody® molecules designed to work together. By selectively targeting cells that express targets for both antibodies, the aim is to maximize treatment potency while minimizing potential toxicity.
HexElect is a combination of two HexaBody molecules designed to work together. By selectively targeting cells that express targets for both antibodies, the aim is to maximize treatment potency while minimizing potential toxicity.
Our novel HexElect® technology platform further builds on our expertise in antibody clustering, and consists of two components designed to work together as a team. By restricting the activation of desired mechanisms of action to cell surfaces co-expressing combinations of two targets, the therapeutic index (the ratio of efficacy to safety) may be improved (Figure 1). In the design of a combination of two HexElect® antibodies, the Fc-mediated activity is decoupled from individual antibody binding events, resulting in a substantial increase in selectivity.
lgG antibodies binding to membrane receptors on cell surfaces have a natural ability to cluster. This clustering may trigger protein- or cell-mediated effector functions like the activation of complement, but can also be leveraged to initiate outside-in signaling pathways in the target cell.¹ Our HexaBody® and HexElect® technology platforms exploit this natural phenomenon to generate potent antibody therapeutics.²
References
1. Diebolder et al., Science 343:1260-1263 (2014)
2. De Jong et al., PLoS Biology 14:e1002344 (2016)
3. Oostindie et al., Nat Biotechnol 40(10):1509-1519 (2022)
HexaElect Glossary
Activation of complement
Binding of the C1q protein to clustered antibodies and the subsequent activation of the C1 complex triggers the activation of the classical complement pathway. The alternative complement pathway is activated spontaneously through hydrolysis of C3, while the lectin pathway is activated upon recognition of carbohydrate structures by the Mannose-Binding Lectin (MBL) receptor or ficolins.
Fc-mediated activity
The immune system’s cellular (e.g., ADCC) and humoral (e.g., CDC) effector systems, which are triggered by the interactions of the Fc-domain of antibodies with Fc receptors on effector cells or the complement factor C1q.
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