Abstract

BACKGROUND: Bacterial superantigen Staphylococcal Enterotoxins (SEs), has stimulated polyclonal T cells irrespective of their antigen specificity, resulted a massive release of cytokines, and suggested that they could be assigned as a candidate of new antitumor agents. Recent attempts have done to specifically target superantigens towards tumors, subsequently Monoclonal antibodies and tumor-related ligands have employed as targeting molecules of superantigen for the preclinical treatment of different tumors. Here, we have evaluated TGFalphaL3-SEB fusion protein as a new antitumor candidate by genetically fusing the third loop of transforming growth factor alpha (TGFalphaL3) to Staphylococcal Enterotoxin type B. METHODS: An in silico techniques have launched to characterize the properties and structure of the protein, before initiating the experimental study, we have predicted physicochemical properties, structures, stability, MHC binding properties and ligand-receptor interaction of this chimeric protein by means of computational bioinformatics tools and servers. RESULTS: Our results have indicated codon adaptation index of tgfalphal3-seb fusion gene has increased from 0.5 in the wild type sequences to 0.85 in the chimeric optimized gene. The mfold data has shown the tgfalphal3-seb mRNA was stable enough for efficient translation in the new host. Based on Ramachandran plot TGFalphaL3-SEB has classified as a stable fusion protein. Our result has shown fusing of TGFaL3 in N-terminal of the TGFalphaL3-SEB construct, had no effects on MHC binding and subsequently superantigenic activity of SEB. Finally based on ligand-receptor docking the binding ability of TGFaL3 was strong enough to its receptor, so TGFalphaL3-SEB could be assigned as a new antitumor candidate in cancer immunotherapy. CONCLUSION: Our results have proposed that TGFalphaL3-SEB was a stable fusion protein with proper affinity to its receptor that overexpressed in various human carcinomas, so it could generate potent immune response towards tumors.