2. Academic Validation
  3. Precision Targeting of Tumor Macrophages with a CD206 Binding Peptide

Precision Targeting of Tumor Macrophages with a CD206 Binding Peptide

  • Sci Rep. 2017 Nov 7;7(1):14655. doi: 10.1038/s41598-017-14709-x.
Pablo Scodeller 1 2,  Lorena Simón-Gracia 3,  Sergei Kopanchuk 4,  Allan Tobi 3,  Kalle Kilk 5,  Pille Säälik 3,  Kaarel Kurm 3,  Mario Leonardo Squadrito 6,  Venkata Ramana Kotamraju 7,  Ago Rinken 4,  Michele De Palma 6,  Erkki Ruoslahti 7 8,  Tambet Teesalu 9 10 11
Affiliations

Affiliations

  • 1 Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14B, Tartu, 50411, Estonia. pablo.david.scodeller@ut.ee.
  • 2 Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 N, Torrey Pines Road, La Jolla, 92097, California, USA. pablo.david.scodeller@ut.ee.
  • 3 Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14B, Tartu, 50411, Estonia.
  • 4 Institute of Chemistry, University of Tartu, Ravila 14, Tartu, 50411, Estonia.
  • 5 Department of Biochemistry, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14B, Tartu, 50411, Estonia.
  • 6 School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Swiss Federal Institute of Technology, Lausanne, CH-1015, Lausanne, Switzerland.
  • 7 Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 N, Torrey Pines Road, La Jolla, 92097, California, USA.
  • 8 Center for Nanomedicine and Department of Cell, Molecular and Developmental Biology, University of California, Santa Barbara Santa Barbara, 93106, California, USA.
  • 9 Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14B, Tartu, 50411, Estonia. tambet.teesalu@ut.ee.
  • 10 Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 N, Torrey Pines Road, La Jolla, 92097, California, USA. tambet.teesalu@ut.ee.
  • 11 Center for Nanomedicine and Department of Cell, Molecular and Developmental Biology, University of California, Santa Barbara Santa Barbara, 93106, California, USA. tambet.teesalu@ut.ee.
PMID: 29116108 DOI: 10.1038/s41598-017-14709-x
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.

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