Anti-tumor Effect Of Superantigen Staphylococcal Enterotoxin B

As potent activator of T lymphocytes, staphylococcal enterotoxins B (SEB ) could directly inhibit tumor cell with MHC-II molecules by superantigen-dependent cellular cytotoxicity, so it has potential therapeutic role for tumor therapy. However, the disadvantages of SEB to induce emesis and cause food poisoning severely limit its clinical application. In this study, we evaluated a series of staphylococcal enterotoxin B mutants including SEB(H12D/H32D), SEB(H105D/H121D), SEB(H12D/H32D/ H105D/H121D), SEB (H32D), SEB (H32Q), SEB (H32L) as an anti-tumor agents in vitro and in vivo. Emetic activity of the proteins in vivo was tested in young cats. We found that two mutants, SEB (H105D/H121D) and SEB(H32Q) with the properties of binding MHC II molecules similar to wild-type SEB, have sharply decreasing emetic and diarrheogenic activity in vivo. when challenged with dose of five-to-ten folds , four out of five cats in the SEB (H105D/H121D) and SEB(H32Q) groups showed no emetic response respectively while in the wt-SEB group, all cats were induced vomiting. Moreover, PBMCs activated by these two proteins are able to induce cytotoxicity towards human carcinoma cell lines SMMC7721 and oral squamous carcinoma cell lines KB and can significantly inhibit their outgrowth at very low concentration. The IC50 of SEB (H32Q) for SMMC-7721 is only 0.798ng/mL. Additionally, treatment of C57BL/6 bearing Lewis lung cancer cells dosed with 125μg/kg leads to a statistically significant decrease in tumor outgrowth and the therapy group shows a tumor necrosis and strong infiltration of lymphocytes in tumor area in SEB (H32Q) group when compared with control group. Our results clearly showed that the genetically modified SEB(H32Q) has lower toxicity and high anti-tumor effect and justifies its further development as interesting candidate for tumor therapy.Because the inhibition effect by superantigen is only limited to MHC II + tumor cells for SDCC depends on MHC II molecules, while the expression levels on many...