Precision Targeting of Tumor Macrophages with a CD206 Binding Peptide

Area of Science:

• Oncology
• Immunology
• Biotechnology

Background:

• Tumor-associated macrophages (TAMs) expressing mannose receptor (CD206/MRC1) promote tumor progression and immunosuppression.
• Targeting these specific TAMs presents an opportunity for novel cancer therapies.

Purpose of the Study:

• To identify and characterize a peptide that selectively targets CD206-expressing TAMs (MEMs).
• To evaluate the peptide's potential for diagnostic imaging and therapeutic delivery in various cancer models.

Main Methods:

• In vivo peptide phage display screens in mice with metastatic breast tumors.
• Deep sequencing to identify enriched peptide sequences.
• In vivo homing studies using fluorescently labeled peptide (FAM-UNO) in multiple cancer models.
• Fluorescence anisotropy assays to confirm CD206 binding.
• Drug-loaded nanoparticle delivery studies.

Main Results:

• The peptide CSPGAKVRC (UNO) was identified and shown to selectively home to MEMs in breast, melanoma, glioma, and gastric cancer models.
• FAM-UNO demonstrated specific binding to CD206 under reducing conditions.
• UNO peptide facilitated the uptake of drug-loaded nanoparticles into MEMs.
• Ex vivo imaging revealed significant accumulation of FAM-UNO in sentinel lymph nodes.

Conclusions:

• The UNO peptide is a promising tool for selectively targeting CD206-expressing TAMs.
• UNO peptide holds potential for developing new diagnostic imaging agents and therapeutic delivery systems for solid tumors.