Macrophages engulf a majority of particles that are injected, whereas our own cells including cancer cells inhibit such phagocytosis by displaying membrane protein CD47. Clinically, anti-CD47 blockade combined with cancer-targeting antibody is now showing efficacy against cancer. Based on our previous study of CD47-derived polypeptides on particles that are phagocytosed minimally compared to control particles, we have now engineered shorter, soluble nano-Self oligopeptides in multivalent form to block CD47’s receptor on macrophages, SIRPα. Bivalent oligos prove more potent as phagocytosis agonists of 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 also suppress a passivating phospho-Tyrosine 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’.

Soluble, multi-valent nano-self peptides 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.