Abstract: The invention relates to superantigen mediated expansion of antigen-specific T cells for cancer and infectious agent treatment/prophylaxis. Mice were injected with inactivated B16F10 mouse melanoma cells, followed by injection with a combined SEA/SEB injection or a sham injection on days 3 and 6, followed by day 4 challenge with live melanoma cells. The SEA/SEB recipient mice survived longer post-challenge and had a higher CTLs against tumor cells than did the sham injected mice. SEA/SEB TCR activation has been reported to be independent of antigen specificity of TCRs. This invention provides a method whereby a combination of Staphylococcal enterotoxin superantigens is used to enhance specific immune responses to activating antigens to enhance immune responses against cancers and infectious agents.