M2 macrophage-associated surface receptor recognized by M2pep (M2pep receptor)

The M2 macrophage-associated surface receptor recognized by M2pep is an unidentified membrane protein selectively expressed on alternatively activated (M2) macrophages, particularly tumor-associated macrophages (TAMs). It was first characterized through the discovery of M2pep (YEQDPWGVKWWY), a peptide identified via subtractive phage display that binds and internalizes into M2 macrophages with high specificity over M1 macrophages and other leukocytes. While the exact molecular identity of the receptor remains elusive, it serves as a critical docking site for targeted delivery systems designed to modulate the tumor microenvironment. Therapeutic strategies leveraging this receptor include the delivery of pro-apoptotic peptides (e.g., M2pep-KLA) to deplete immunosuppressive TAMs or the use of M2pep-conjugated nanoparticles to deliver gene-silencing agents (e.g., siRNA against CSF-1R) for macrophage reprogramming. Targeting this receptor has shown promise in preclinical models of colon carcinoma, breast cancer, and melanoma by reducing tumor growth and improving survival. However, challenges remain regarding the peptide's relatively low binding affinity and its primary selectivity for murine rather than human M2 macrophages.

Other names

M2pep binding partnerM2 macrophage-targeting peptide receptorM2 macrophage surface receptor

Targeted depletion of M2 macrophages and reprogramming of tumor-associated macrophages (TAMs) via intracellular delivery of therapeutic payloads.