Staphylococcal enterotoxin G and I: augmenting the T cell response to murine melanoma.

Abstract

Abstract Staphylococcal enterotoxins (SEs) have been shown to be effectual proteins which demonstrate anti-tumor activity. SEG and SEI, produced from the enterotoxin gene cluster (egc) of Staphylococcal aureus, activate T cells with Vβ specificity to elicit robust T cell proliferation, T helper cell 1 (TH1) and TH2 cytokine secretion, and nitric oxide dependent tumor lysis. Our data highlight the effects of SE stimulated T cells and the subsequent consequence on aggressive, metastatic cancer progression using B16-F10 murine melanoma model. Specifically, we explore the differences between major histocompatibility complex (MHC) and human leukocyte antigen (HLA) SE presentation to the T cells via the T cell receptor (TCR). Our data demonstrates increased survival of B16-F10 tumor bearing mice, C57BL/6 and DQ8 (HLA-DQA1*0301, HLA-DQB1*0302) transgenic mice, after irradiated B16-F10 vaccination and SE stimulation. Interestingly, SEG and SEI induce strong T cell proliferation yet do not induce neutralizing antibodies to the extent of classical SEs, SEA and SEB, nor induce autoimmune pathology. Our findings demonstrate that superantigen administration enhances lymphocytic tumor killing and suggest a potential role for SEG and SEI as potent immunotherapeutics for human cancer.