Precision Targeting of Tumor Macrophages with a CD206 Binding Peptide

Abstract

Tumor-associated macrophages (TAMs) expressing the multi-ligand endocytic receptor mannose receptor (CD206/MRC1) contribute to tumor immunosuppression, angiogenesis, metastasis, and relapse. Here, we describe a peptide that selectively targets MRC1-expressing TAMs (MEMs). We performed in vivo peptide phage display screens in mice bearing 4T1 metastatic breast tumors to identify peptides that target peritoneal macrophages. Deep sequencing of the peptide-encoding inserts in the selected phage pool revealed enrichment of the peptide CSPGAKVRC (codenamed “UNO”). Intravenously injected FAM-labeled UNO (FAM-UNO) homed to tumor and sentinel lymph node MEMs in different cancer models: 4T1 and MCF-7 breast carcinoma, B16F10 melanoma, WT-GBM glioma and MKN45-P gastric carcinoma. Fluorescence anisotropy assay showed that FAM-UNO interacts with recombinant CD206 when subjected to reducing conditions. Interestingly, the GSPGAK motif is present in all CD206-binding collagens. FAM-UNO was able to transport drug-loaded nanoparticles into MEMs, whereas particles without the peptide were not taken up by MEMs. In ex vivo organ imaging, FAM-UNO showed significantly higher accumulation in sentinel lymph nodes than a control peptide. This study suggests applications for UNO peptide in diagnostic imaging and therapeutic targeting of MEMs in solid tumors.

The effect of intranasally administered TLR3 agonist larifan on metabolic profile of microglial cells in rat with C6 glioma

“…According to general ideas, these cells are not efficient at antigen presentation, and express low levels of MHC a co-stimulatory molecules. In accordance with data from different research groups, they can exibit reduced or augmented phagocytic activity along with up-regulated expression of M2 phenotypic markers such as the mannose receptor (CD206) and the hemoglobin/haptoglobin scavenger receptor (CD163) [29,30].…”

Application of Polymersomes Engineered to Target P32 Protein for Detection of Small Breast Tumors in Mice

“…The scans acquired at 6 h showed uptake of both targeted and non-targeted polymersomes in the liver ( Figure 3A Figure 4B). We have shown in a recent publication that an insignificant portion of the peptide is released from PEG-PCL polymersomes incubated with the serum of the 4T1 tumor bearing mice for 6 h [33]. We suggest that the high excretion at short time points observed is due to the renal clearance of the 1 0…”

“…To study the macrophage uptake of LinTT1-PS, sections of tumors and organs were immunostained with antibodies against CD68, CD11b, and CD206 markers. CD68 and CD11b are pan-macrophage markers that label normal macrophages (including macrophages in spleen, lung, and in Kupffer cells in liver [33]), and TAMs [35]. CD206 is a marker of pro-tumor M2 macrophages [36], which promote tumor growth [37].…”

Progress on Modulating Tumor‐Associated Macrophages with Biomaterials

“…Another peptide, UNO, binds CD206 (mannose) receptor on TAMs with high specificity (>95%) across five tumor models of breast carcinoma, melanoma, glioma, and gastric carcinoma . Significantly, UNO did not home to nonmalignant tissues, even those with CD206 + macrophages, or accumulate nonspecifically in regions with vascular leakiness.…”