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Introduction: The goal of vaccine researchers has been induction of a specific and active immune response, which offers patients cancer therapy with limited toxicity and long-standing protection. There have been great strides made toward this goal, as evidenced by the recent FDA approval of Sipuleucel-T (Provenge). The simplest, most efficacious and most affordable vaccine strategy, however, remains an area of great debate. Multiple strategies exist, varying by number and type of target, as well as delivery method. Main Idea: There have been great advances in immunotherapy for the treatment of cancer in the last decade. The clinical success of recently FDA approved ipilimumab in advanced melanoma demonstrates the strength of the immune system in treating cancer. This monoclonal antibody, through CTLA-4 blockade, uses a non-specific activation of the immune system, augmenting the natural immune response to tumors by decreasing T cell inhibition. Monoclonal antibodies are a type of passive immune therapy, which does not induce immune memory and, thus, offers no ongoing immune protection after completion of therapy. The goal of cancer vaccine researchers has been to achieve specific stimulation of active immunity, which should offer both safety and long-standing benefit. The recent FDA approval of Sipuleucel-T (Provenge), the first cancer vaccine to achieve such approval, has sparked renewed enthusiasm for the potential of cancer vaccines. One approach is a DNA vaccine which involves injection of a bacterial plasmid that encodes the desired antigen. This antigen is then produced by the host cell. This strategy again uses the body’s machinery to process and present the desired immunogenic peptide. This strategy can be easily monitored with immunologic assays that can identify specific immune responses against the target peptide. It again relies, however, on often unreliable and inefficient mechanisms of antigen processing and presentation without a real sense of the amount of effective epitope presentation that is taking place. In order to more efficiently stimulate immune responses against a specific immunogenic peptide, many researchers have advocated for giving the peptide itself as a vaccine. The most effective method of delivering this peptide, however, continues to be widely debated. One popular method is dendritic cell (DC)-mediated vaccines. This strategy involves drawing a patient’s blood, isolating and artificially maturing circulating monocytes into DCs, then priming them against an immunogenic peptide(s). The high costs of cell-mediated vaccines make a cancer vaccine that is more easily produced and with a larger target population more commercially appealing, particularly in a time of increased scrutiny of the cost of healthcare. A simpler approach is a peptide-based vaccine, which combines an immunogenic peptide and an immune-adjuvant in one solution, which is then injected subdermally. Peptide vaccines have been shown repeatedly to induce a specific and sometimes long-lasting response by the immune system, both in vitro and in vivo. Despite this encouraging immunologic data, clinical response rates have been inconsistent, fueling the debate over how best to administer peptide vaccines. One area of debate has been which class of MHC molecules and, therefore, which population of T cells, must be targeted in order to elicit an effective response. In conclusion, there is great interest in the use of the immunotherapy to treat malignancy. There are numerous approaches to this interesting clinical problem, and it is likely that there will be roles for many, but the simplicity and potential broad applicability of peptide vaccines make this strategy particularly enticing. Author works for OMICS Publishing Group, which is built upon the principles of Open Access Journals and is determined to provide free and unrestricted access of research articles to scientists around the world for the advancement of science and technology. You can view our Bioinformatics Journal for more related information.
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Peptide vaccine, cancer, immunotherapy, DNA, bioinformatics,
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