IDD-3

Cancer vaccine is an intervention for therapeutic or prophylactic option by activating antitumor immune responses in vivo. Vaccine to human papillomavirus is clinically available, which prevents women from developing cervical cancer. Therapeutic cancer vaccines have been studied in randomized clinical trials. Melanoma vaccine using a gpl00 -peptide has been analyzed in recurrent disease patients. Patients treated with peptide vaccine with high-dose IL-2 lived longer than those with IL-2 alone. Another clinical trial covered hormone-resistant prostate cancer patients who were treated with dendritic cell (DC) vaccine of prostate-acid protein plus GM-CSF. DC-vaccinated patients significantly lived longer than those with placebo, though no difference of disease progression was seen between the two groups. Worldwide phase III study of MAGE-A3 vaccine for non-small cell lung cancer has been initiated. Its analysis on clinical benefits will be expected. Vaccine therapy for cancer would be another option for clinical practice in near

Immunosuppressive factors, such as vascular endothelial growth factor, transforming growth factor-β, prostaglandin E2, interleukin (IL)-10, and IL-6, are made frequently by cancer cells. These factors, along with others, can inhibit the development and function of tumor-reactive effector T cells and the clinical results of cancer vaccines. Production of these factors by tumor cells is associated with disease progression and may represent an active immune surveillance escape mechanism. However, a number of factors appear to be made directly in response to signaling molecules, such as RAS, AKT, and signal transducer and activator of transcription 3, which are activated as a result of genetic events that occur during oncogenesis. Methods to overcome the negative effects of immunosuppressive factors, which are “hard wired” into gene programs of cancer cells, might then improve the results of cancer vaccines. For example, specific blocking antibodies, which recognize such factors, or kinase inhibitors, which block the signaling pathways that lead to their production, could potentially be used as vaccine adjuvants. The effects of immunosuppressive factors may also be “turned off” by cytokines with tumor suppressor properties. The enhanced clinical and immunological effects of melanoma vaccines observed after the administration of high doses of interferon-α2b provide a “proof of principle” in human patients, that agents which counter the gene programs of cancer cells, causing them to intrinsically resist tumor-reactive T cells, may improve significantly the efficacy of cancer vaccines.