UNO peptide

Tumor-associated macrophages (TAMs) have been linked to the tumor progression and suppress anti-tumor immunity. Number of TAMs in human tumors correlate with a higher tumor grade and shortened survival for several cancer types. In particular, the perivascular macrophages in tumors have been associated with increased tumor angiogenesis, distant metastasis, poor prognosis, and/or the recurrence of tumors after chemotherapy in various forms of cancer. To identify peptides binding the peritoneal cells of 4T1 breast cancer bearing mice, Teesalu and colleagues performed a phage screen by injecting the CX7C peptide library to the peritoneum of tumor-bearing or healthy mice. After 2 h, the peritoneal cells were isolated, the bound phage were rescued by amplification and subjected to high-throughput sequencing. The CSPGAKVRC peptide (UNO) was the most frequent non-truncated peptide in the pool amplified from the tumor-bearing mice. The GSPGAK motif was detected in physiological ligands of CD206, a marker of M2-skewed macrophages. The authors then showed that UNO bound to the CD206, but interestingly the binding required linearity of the UNO peptide. It was concluded that the glutaredoxin system in the tumor microenvironment may contribute to the reduction of the disulfide-bridged UNO. Intravenously injected fluorescent UNO (FAM-UNO) accumulated in the CD206+ macrophages in 4T1 tumors and in sentinel lymph nodes. In addition, FAM-UNO recognized the CD206+ macrophages in several other tumor models such as intracranial glioblastoma (WT-GBM), metastatic melanoma (B16F10), and peritoneal gastric carcinoma (MKN45-P). Moreover, FAM-UNO was shown to guide cargo to CD206+ macrophages and was proposed as a potential sentinel lymph node imaging agent.