Whole cell vaccines--past progress and future strategies.

Cancer vaccines have shown success in curing tumors in preclinical models. Accumulating evidence also supports their ability to induce immune responses in patients. In many cases, these responses correlate with improved clinical outcomes. However, cancer vaccines have not yet demonstrated their true potential in clinical trials. This is likely due to the difficulty in mounting a significant anti-tumor response in patients with advanced disease because of pre-existing tolerance mechanisms that are actively turning off immune recognition in cancer patients. This review will examine the recent progress being made in the design and implementation of whole cell cancer vaccines, one vaccine approach that simultaneously targets multiple tumor antigens to activate the immune response. These vaccines have been shown to induce antigen-specific T-cell responses. Preclinical studies evaluating these vaccines given in sequence with other agents and cancer treatment modalities support the use of immunomodulating doses of chemotherapy and radiation, as well as immune-modulating pathway-targeted monoclonal antibodies, to enhance the efficacy of cancer vaccines. Based on emerging preclinical data, clinical trials are currently exploring the use of combinatorial immune-based therapies for the treatment of cancer.