ABSTRACT
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 TGF alpha L3-SEB fusion protein as a new antitumor candidate by genetically fusing the third loop of transforming growth factor alpha [TGF alpha L3] to Staphylococcal Enterotoxin type B. 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. Our results have indicated codon adaptation index of tgf alpha l3-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 tgf alpha l3-seb mRNA was stable enough for efficient translation in the new host. Based on Ramachandran plot TGF alpha L3-SEB has classified as a stable fusion protein. Our result has shown fusing of TGFalphaL3 in N-terminal of the TGF alpha L3-SEB construct, had no effects on MHC binding and subsequently superantigenic activity of SEB. Finally based on ligand-receptor docking the binding ability of TGFalphaL3 was strong enough to its receptor, so TGF alpha L3-SEB could be assigned as a new antitumor candidate in cancer immunotherapy. Our results have proposed that TGF alpha L3-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