Emerging melanoma vaccines

No satisfactory treatment currently exists for melanoma once it has spread beyond its original site. At present, the only FDA-approved treatment for advanced melanoma is IFN-alpha2b. Vaccines are an experimental therapy intended to stimulate the immune system to react more strongly against patients' own melanoma cells, thereby destroying the tumour or slowing its progression. Unfortunately, the exact tumour antigens that can stimulate an effective tumour-protective response in humans remain unknown. The approach that is increasingly followed to circumvent this problem is to prepare polyvalent vaccines containing a variety of melanoma antigens, as the greater the number of antigens in a vaccine, the greater the chance it will contain the correct antigen(s) to stimulate an antitumour response. Two recent randomised trials suggest that this approach results in vaccines that can be clinically effective. One is a double-blind, placebo-controlled trial of a polyvalent, shed antigen melanoma vaccine developed by Bystryn and licenced to NeoVac; the other is a larger randomised trial of Melacine (Corixa Corp.), a vaccine prepared from the lysate of two melanoma cell lines adjuvanted with Detox, which was developed by Mitchell and commercialized by Corixa. In both cases, tumour progression was delayed in the vaccine-treated patients, although in the latter trial, this was only observed in patients with certain human leukocyte antigen phenotypes. Several other vaccines are currently in Phase III trials, but the results of these trials are still pending. The major issues that need to be addressed are designing more effective melanoma vaccines with a mix of melanoma-associated antigens that can stimulate clinically beneficial antitumour immune responses, and finding an adjuvant that can safely, easily and powerfully boost the frequency and magnitude of these responses.