Immunotherapy of malignant melanoma

Several areas of immunotherapeutic research may ultimately improve the effectiveness of active specific immunotherapy for melanoma and other malignancies. Identification of the most relevant tumor antigens will continue to be a vital component of vaccine design. Optimizing delivery of these antigens by use of adjuvants, dendritic cells, or heat shock proteins will enhance the immunogenicity of vaccines. The use of DNA vaccines to deliver nucleotides that encode relevant antigens and immunologic molecules, such as costimulatory molecules, and the use of targeted therapy with immunocytokines have yielded promising results in animal studies. Finally, cutting-edge techniques such as quantitative polymerase chain reaction and gene/protein microarrays will be used to monitor the response to a vaccine and thereby guide management decisions. Although IFN-alpha 2b is the only FDA-approved adjuvant treatment for AJCC stage IIB/III melanoma, recent data failed to show a benefit in overall survival. For patients with AJCC stage IV melanoma, chemotherapy with dacarbazine is currently the standard of care, with modest response rates of 15% to 20%. The encouraging response rates and low toxicities that were reported in phase I/III trials suggest that active immunotherapy may prove to be the most effective adjuvant therapy. At present, there are no FDA-approved cancer vaccines for malignant melanoma, and the results of ongoing randomized phase III clinical trials are greatly anticipated.