Repeated treatment with S. aureus superantigens expands the survival rate of Ehrlich ascites tumor bearing mice.

The bacterial superantigen Staphylococcal enterotoxin-A (SEA), produced by some strains of Staphylococcus aureus, causes proliferation of cytotoxic T-lymphocytes and cytokine production in vivo. SEA has been shown to be highly efficient for antibody-targeted superantegen immunotherapy for different tumor models. A candidate B-cell superantigen that has received considerable attention these days is staphylococcal protein-A (PA). It has been shown to possess multiple immunological responses. The anti-tumor property of PA is well documented in the literature in various transplantable tumors of rats and mice. In the present study, we have shown that the T-cell superantigen SEA and B-cell superantigen PA induce immunomodulatory and anti-tumor activity which is strongly protentiated by PA + SEA co-administration. Combination treatment with PA and SEA prolongs the immune response in vivo, limits the development of immunological unresponsiveness and promotes maximum anti-tumor effects to tumor carrying animals, as compared with PA or SEA alone. The immune response after combined therapy is characterized by substantially augmented IFN-gamma, TNF-alpha, Nitric oxide and strong CTL activity. Our data demonstrate that combined PA + SEA therapy induces long-term survival of the animals, carrying the Ehrlich ascites tumor.

Superantigen-induced apoptotic death of tumor cells is mediated by cytotoxic lymphocytes, cytokines, and nitric oxide.

The bacterial superantigen staphylococcal enterotoxin A (SEA) is a potent inducer of CTL activity and cytokine production in vivo. Protein A (PA) of Staphylococcal aureus has been found to have diverse biological response modifying properties and to possess antitumor, antitoxic and antiparasitic effects. In this study we examined the anti-tumor effect of these two superantigens used separately as well as in combination in mice carrying the Ehrlich ascites tumor. With combined treatment, DNA cell cycle analysis of tumor cells showed a significant (P < 0.05) percentage of tumor cell death. Levels of the soluble mediators TNF-alpha, IFN-gamma and IL-1 as well as NO were elevated. Additionally, CD4(+) and CD8(+) specific T cells in spleen, thymus and PBMC in tumor carrying mice were increased (P < 0.01). Our data altogether suggests that enhanced tumor cell death is caused by the increased CTL activity, cytokine and nitric oxide levels, in response to the combined effect of SEA + PA.