In Silico Design and Analysis of TGFαL3-SEB Fusion Protein as “a New Antitumor Agent” Candidate by Ligand-Targeted Superantigens Technique

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 tgf?l3-seb fusion protein as a new antitumor candidate by genetically fusing the third loop of transforming growth factor alpha (tgf?l3) 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 tgf?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?l3-seb mrna was stable enough for efficient translation in the new host. based on ramachandran plot tgf?l3-seb has classified as a stable fusion protein. our result has shown fusing of tgfal3 in n-terminal of the tgf?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 tgfal3 was strong enough to its receptor, so tgf?l3-seb could be assigned as a new antitumor candidate in cancer immunotherapy.conclusion: our results have proposed that tgf?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.