Human tumors actively suppress and inhibit effective immunity. Work from our group, and others, has shown that MHC class II restricted, CD4+ IFN-gamma secreting Th1 cells may be essential for tumor rejection. A major goal of the CVI is the development of vaccines that specifically elicit and expand Type I T-cells to treat and prevent cancer. Our therapeutic and prophylactic DNA and peptide-based vaccines target multiple overexpressed tumor associated proteins thought to drive transformation, growth, and metastasis. We have discovered immune dominant protein segments called ‘epitopes,’ that preferentially stimulate anti-tumor IFN-gamma/Th1 responses and other epitopes within self proteins that may suppress Type I immunity. Our studies have shown that including immune stimulatory epitopes, while excluding immune suppressive segments, will create optimum anti-cancer vaccines. Our multi-antigen, multi-epitope approach aims at heading off tumor escape by avoiding immune suppression and targeting multiple tumor growth pathways. We currently have vaccines for breast, ovarian, colon, lung, sarcoma, bladder, and prostate cancers, that are at various stages ranging from discovery through Phase II clinical trials.