Vaccine therapy for cancer

Background: Tumor-specific cytotoxic T-lymphocytes (CTLs) can be isolated from the solid tumors, draining lymph nodes, metastatic effusions, and peripheral blood of cancer patients. Despite this evidence for a cell-mediated immune response to cancer, attempts at active specific immunotherapy using cancer vaccines have met with little success in clinical trials. Methods: We have reviewed the immunobiology of the cell-mediated immune response to cancer by focusing on what is known about the major histocompatibility complex (MHC)-restricted interaction between tumor cells and CD8⁺ or CD4⁺ T-cells. In addition, we review the recent advances in the identification of tumor-associated antigens (TAAs) that are recognized by tumor-specific CTLs in melanoma and other cancers. In discussing these antigens, we highlight the recent identification of several MHC-restricted antigenic peptides that are recognized by CTLs from patients with melanoma and those with ovarian and breast cancer. We examine the implications that the discovery of these TAAs and peptides will have on the development of new anticancer vaccines. We review the most recent vaccine trials in melanoma and other cancers and focus on current concepts aimed at improving the therapeutic efficacy of future vaccines, including genetically engineered tumor cell vaccines. Conclusions: With the recent identification of several TAAs and antigenic peptide epitopes in melanoma and other cancers, immunotherapy researchers are now focusing on new strategies for the development of anticancer vaccines. As the repertoire of known TAAs increases and our understanding of the immunobiology of cell-mediated immunity to cancer improves, immunotherapists remain cautiously optimistic in their quest for effective cancer vaccines.