Injections of foreign particles generally lead to non-specific serum adsorption with a corona rich in antibody (IgG) that binds and activates phagocytosis by macrophages. Our own cells and cancer cells inhibit such phagocytosis by displaying ‘marker of self’ CD47. While clinical combination of cancer-targeting antibodies with anti-CD47 blockade shows some efficacy against cancer, safety of these therapies remains controversial. Based on our previous study of CD47-derived polypeptides that mimic the binding and function of full length CD47, we engineer soluble nano-Self oligopeptides in multivalent form to block CD47’s receptor on macrophages, SIRPα. Bivalent nano-Self agonists prove more potent in phagocytosing antibody-targeted cells (<i>K</i><sub>eff</sub> ~ 20 nM) than monovalent oligos. Bivalents also exhibit a more stable hairpin-like structure and out-compete monovalents in macrophage association, whereas scrambled oligos lack function. Soluble nano-Self oligos added to isolated macrophages suppress a passivating phosphotyrosine signal, consistent with ‘self’ signaling through SIRPα. Bivalent nano-Self oligopeptides are thus a potential alternative to anti-CD47 blockade and promoting phagocytosis of ‘self’.

Multi-valent nano-self peptides suppress self-signaling and increase phagocytosis of antibody-opsonized targets

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.