Human CD47-Derived Cyclic Peptides Enhance Engulfment of mAb-Targeted Melanoma by Primary Macrophages

CD47 on healthy cells, cancer cells, and even engineered particles can inhibit phagocytic clearance by binding SIRP alpha on macrophages. To mimic and modulate this interaction with peptides that could be used as soluble antagonists or potentially as bioconjugates to surfaces, we made cyclic nano-Self peptides based on the key interaction loop of human CD47. Melanoma cells were studied as a standard preclinical cancer model and were antibody-opsonized to adhere to and activate engulfment by primary mouse macrophages. Phagocytosis in the presence of soluble peptides showed cyclic > wildtype > scrambled activity, with the same trend observed with human cells. Opsonized cells that were not engulfed adhered tightly to macrophages, with opposite trends to phagocytosis. Peptide activity is nonetheless higher in human versus mouse assays, consistent with species differences in CD47-SIRP alpha. Small peptides thus function as soluble antagonists of a major macrophage checkpoint.

Automated summary

The expression of CD47 on healthy cells, cancer cells, and engineered particles can inhibit phagocytic clearance by binding SIRP alpha on macrophages. In this study, cyclic nano-self peptides were synthesized to mimic and modulate this CD47-SIRP alpha interaction. These peptides showed high antagonistic activity and could act as soluble antagonists of a major macrophage checkpoint.