Session: Current Topics in Biological Chemistry:

Macrophage engulfment of both healthy and cancer cells is inhibited by the expression of membrane protein CD47 on their surface which binds to the macrophage immune checkpoint receptor SIRPα to signal 'self'. We have designed multivalent, nano-Self CD47-derived peptides that inhibit SIRPα binding and function. Bivalent and tetravalent peptides are more potent than antibody and monovalent 8-mers controls as agents for phagocytosis of antibody targeted cancer cells. Soluble CD47 binding to human macrophages is outcompeted by multivalent peptides, consistent with SIRPα binding, and also suppress phosphotyrosine in macrophages, consistent with inhibition of ‘self’ signaling through SIRPα. Pre-clinical studies in mice indicate safety, with no anemia or weight loss. Multivalent nano-Self peptides thus constitute an alternative approach to antibody-based CD47 blockade in promoting phagocytosis of ‘self’ – including cancer cells targeted clinically.

David Chenoweth

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