We have tested allogeneic
melanoma cell lysates as active immunotherapy, originally in stage IV patients to determine their safety and immunologic effectiveness. Surprisingly, phase I and II trials with frozen lysates showed a 20% objective response rate, with 8% long-term survivors.
Melacine (Ribi ImmunoChem Research, Hamilton, MT), a lyophilized preparation from the same two cell lines, has been tested nationally and has caused regressions in approximately 10% of patients. Long-term stabilization of disease was noted in 10% to 20% of patients in all trials. A multicenter phase III comparison of low-dose
cyclophosphamide plus
Melacine versus four-
drug chemotherapy showed no difference in response rates and survival, with fewer and milder side effects due to
Melacine. In our single-arm trial in resected stage III disease, the overall survival rate (66-month median follow-up) is 66%, with a median relapse-free survival time of 36 months.
Interferon-alfa 2b (IFN-alpha) given to patients failing to respond to
Melacine elicited major objective responses in a larger proportion than anticipated with IFN-alpha alone. These results stimulated current multicenter trials in stage IV and resected stage III
melanoma of
Melacine and IFN-alpha in combination versus IFN-alpha alone. Of scientific note were (I) identification of a new
melanoma antigen from a gene (MG50) isolated from one of the immunizing cell lines, and (2) demonstration that a new
melanoma arising in 1995 in a long-term survivor was immunologically and genetically distinct from her original 1986
tumor. While it is important to define which
epitopes are involved, multiepitopic (polyvalent) mixtures have established the
therapeutic effect of
melanoma vaccines.