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Rob de Jong

Rob de Jong | The Antibody Series 2024

Dr. Rob N. de Jong has worked in different roles at the biotechnology company Genmab since 2007, related to molecular biology, CMC-supportive research, and protein engineering. Currently, Rob leads Genmab’s Antibody Format Development efforts, where his team marries rigorous science with playful protein engineering to address unsolved therapeutic challenges. His team applies biomolecular and structural insights to create novel therapeutic antibody platform technologies.

Rob is an inventor of Genmab’s HexaBody® and HexElect® technologies, and after a workday of brewing ideas, he enjoys cooking Szechuanese dishes at home.

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Lecture

Single molecule studies and applications of antibodies engineered to induce cell surface-restricted hexamerization

lmmunoglobulin G (lgG)-mediated clustering of membrane receptors naturally occurs on cell surfaces to trigger complement- or cell-mediated effector functions or to initiate intracellular signaling. Our HexaBody platform based on engineered antibody multimerization is applied in multiple investigational products currently in clinical development.

  • To understand this process at single molecule detail, we collaborated with Diane Lidke and her team at the University of New Mexico and supplemented single particle tracking, single molecule FRET, and dSTORM super resolution microscopy with functional characterization.
  • We demonstrate how antibody and antigen cell surface abundance, antibody multimerization and the recruitment of complement component C1q form coupled, dynamic equilibria on cells.

We discuss how antibodies can be engineered to manipulate these equilibria to promote the cell-surface restricted multimerization of antibodies with a single specificity, or to restrict the hetero-multimerization of engineered antibody pairs with different specificities to cells that co-express specific target combinations of interest.

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This presentation and others can be viewed on-demand for free.