Seminar series - Anthony Rullo

Title: Covalent "Proximity-Induction" Strategies to Modulate Ligand-Receptor Interactions for Immunoncology

Abstract: A major class of tumor immunotherapeutics function by bridging immune machinery with tumor antigens, highly expressed on cancer cells compared to normal tissue. Antibody recruiting molecules represent an emerging synthetic immunotherapeutic strategy to bridge serum antibodies with these tumor antigens, leading to Fc receptor mediated anti-tumor function. In this seminar, we describe the development of a new medicinal chemistry strategy that uses covalent chimeric molecules, to enhance antibody recruitment to cancer cells. The covalent engagement of serum antibodies affects unique anti-tumor functional enhancements, generating new hypotheses surrounding mechanisms of immune receptor activation. More generally, covalency may represent a strategic tool to modulate the kinetics of immune receptor interactions directly, without intermediary antibodies. This has special utility for mechanistic interrogation of receptor pharmacology and the development of novel covalent tumor immunotherapeutic drugs and targeting strategies.