Project 466842

Cancer immunotherapy works by using the bodys own immune system to treat cancer. A type of immunotherapeutic known as ;molecular adapters work by binding immune cells and linking them to targeted tumour cells, allowing the immune cells to kill the tumour cells. One way that immune cells kill is through phagocytosis, which is activated by the clustering of Fc receptors on the cell surface. How molecular adapters interact with immune receptors to modulate receptor clustering is unknown. We hypothesize that the efficacy of Fc clustering and the resultant anti-tumour response of molecular adapters depend on the number, spatial array, and stability of interactions between the molecular adapters and the receptors. We will use a synthetic, multivalent DNA scaffold that can precisely tune these parameters to investigate their effects on immune cell activation. The DNA scaffold will have CP33, a peptide known to bind the humanFcγRI immune receptor, anchored to it at selected locations using click chemistry. We plan to synthesize several different scaffolds that will bind a different number ofFcγRI receptors and hold those receptors at different distances apart on the cell surface. We will then use immunobiological flow cytometry assays the asses the level of immune cell activation that results from treatment with the different scaffolds. These findings will not only further our understanding of how the anti-tumour response of molecular adapters is impacted by the interactions between the molecular adapters and immune cell receptors, but they can also be used to guide future immunotherapeutic design. The CP33 peptide can be easily replaced by novel peptides that bind other immune receptors, allowing this platform to be adapted to study different receptors in future research.