Targeting of hepatoma cell and suppression of tumor growth by a novel 12mer peptide fused to superantigen TSST-1.
Hepatocellular carcinoma (HCC), one of the most common and malignant tumors worldwide, is unresponsive to any of the available therapies. Using intact HCC cells as therapeutic targets, we isolated a novel peptide, denoted HCC79 (KSLSRHDHIHHH), from a phage display peptide library. HCC79 can bind to hepatoma cell membranes with high affinity and specificity. Remarkably, competitive binding assays demonstrated that HCC79 competed with HAb25, a specific antibody for HCC, in binding to hepatoma cells. The corresponding synthetic peptide did not inhibit tumor proliferation directly, but repressed tumor invasion significantly in a cell migration assay. Moreover, we explored the potential of the selected peptide to deliver a superantigen (SAg) to cancer cells, to attain a significant cell-targeting effect. When the peptide is fused to the TSST-1 SAg, the resulting fusion protein could bind to hepatoma cells with high affinity in vitro and improved the tumor inhibition effect by activating T lymphocyte cells in vitro and in vivo, compared with TSST-1 alone. Taken together, our results indicate that this peptide and its future derivatives may have the potential to be developed into highly specific therapeutic agents against cancer.
Jiang
Yong-Qiang
YQ
National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Science, Peking University, Beijing, China.
Wang
Hai-Rong
HR
Li
Han-Ping
HP
Hao
Huai-Jie
HJ
Zheng
Yu-Ling
YL
Gu
Jun
J
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use*; D001667:Binding, Competitive; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D019151:Peptide Library; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D018089:Superantigens / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D004768:Enterotoxins; D010446:Peptide Fragments; D019151:Peptide Library; D011993:Recombinant Fusion Proteins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal