Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Antibodies, Monoclonal / metabolism
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Bacterial Toxins / genetics
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Bacterial Toxins / immunology
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Bacterial Toxins / isolation & purification
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Bacterial Toxins / metabolism
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Bacterial Toxins / therapeutic use*
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Binding, Competitive
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Carcinoma, Hepatocellular / immunology*
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Carcinoma, Hepatocellular / pathology
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Carcinoma, Hepatocellular / therapy*
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Enterotoxins / genetics
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Enterotoxins / immunology
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Enterotoxins / isolation & purification
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Enterotoxins / metabolism
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Enterotoxins / therapeutic use*
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Liver Neoplasms / immunology*
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Liver Neoplasms / pathology
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Liver Neoplasms / therapy*
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Lymphocyte Activation / drug effects
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Peptide Fragments / chemistry
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Peptide Fragments / pharmacology*
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Peptide Library
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Protein Binding
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Recombinant Fusion Proteins / immunology
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Recombinant Fusion Proteins / therapeutic use
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Superantigens / genetics
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Superantigens / immunology
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Superantigens / isolation & purification
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Superantigens / metabolism
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Superantigens / therapeutic use*
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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Tumor Cells, Cultured
Substances
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Antibodies, Monoclonal
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Bacterial Toxins
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Enterotoxins
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Peptide Fragments
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Peptide Library
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Recombinant Fusion Proteins
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Superantigens
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enterotoxin F, Staphylococcal