Application Superantigen Staphylococcus Aureus Enterotoxin (a) Mutant Tumor Cell Apoptosis Induced By Cellular Immunity

As potent activators of T lymphocytes, staphylococcal enterotoxins (SEs) have a potential to be used in tumor therapy. However, the disadvantages that Staphylococcal enterotoxins induce emesis and causes food poisoning limit its clinical application. In this study, we evaluated a Staphylococcal Enterotoxin A mutant (SEA-H61D) as an anti-tumor agent in vitro and in vivo. This mutant was defective in emetic activity but maintained the ability to stimulate T-cell proliferation. Monkeys, rabbits and mice are tolerated to SEA-H61D challenge when administered systemically. SEA-H61D-activated PBMCs are able to induce cytotoxicity towards various human carcinoma cells in co-culture experiments in vitro. SEA-H61D could significantly inhibit the outgrowth of most of the cancer cell lines tested at very low concentrations. Additionally, treatment of C57 mice with doses of SEA-H61D ranging from 125 to 500 μg/Kg results in activation of CD4~+, CD8~+ T lymphocytes. Systemic treatment of tumor in different mouse models with SEA-H61D results in a statistically significant decrease in tumor outgrowth. Moreover, the therapy group shows a tumor necrosis and strong infiltration of lymphocytes in tumor area in contrast to control group. The toxicity of SEA-H61D is trivial even administered systemically during the treatment. These preclinical results suggest that SEA-H61D might be a promising candidate as an anti-cancer agent for further clinical evaluation.