Perspective on allogeneic melanoma lysates in active specific immunotherapy.
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.
Mitchell
M S
MS
Center for Biological Therapy and Melanoma Research, University of California San Diego Cancer Center, La Jolla 92093-0061, USA.
D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000939:Epitopes; D006801:Humans; D016233:Immunotherapy, Active; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic; D014407:Tumor Cells, Cultured; D017778:Vaccines, Combined
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D000939:Epitopes; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C116434:Melacine; D011994:Recombinant Proteins; D017778:Vaccines, Combined; C094534:polyvalent melanoma cell vaccine