Polyvalent melanoma cell vaccine induces delayed-type hypersensitivity and in vitro cellular immune response.
Patients with melanoma metastatic to distant sites or at high risk for recurrent melanoma have been treated with a polyvalent melanoma cell vaccine (MCV) in phase II protocols. We assessed in vivo and in vitro cell-mediated responses to MCV in 163 patients who had undergone surgical resection of American Joint Committee on Cancer stage III melanoma. During the first 4 months of vaccine immunotherapy, 135 patients (83%) responded by developing a positive delayed-type hypersensitivity reaction > or = 6 mm to MCV. In a mixed lymphocyte tumor cell reaction using peripheral blood lymphocytes, 35 of 42 patients (83%) showed a recall proliferative response to one or more of the three cell lines of MCV. There was a significant correlation between delayed-type hypersensitivity reaction and mixed lymphocyte tumor cell reaction (P = 0.013). After 4 months of MCV therapy, 8 of 11 patients had an increased mixed lymphocyte tumor cell reaction to autologous melanoma cells. During the first 4 months of vaccine therapy, 16 of 33 patients developed more than a 50% increase in cytotoxic T-cell activity against one of the cell lines of MCV. Overall survival was significantly prolonged in patients with a positive delayed-type hypersensitivity reaction (P = 0.0054) and/or increased cytotoxic T-cell activity (P = 0.02). These findings suggest that MCV induces specific T-cell responses which are correlated with clinical course; the data also suggest that some of these responses are directed against autologous melanomas and may play a major role in controlling the progression of melanoma.
John Wayne Cancer Institute at Saint John's Hospital and Health Center, Santa Monica, California 90404.
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A
Barth
D S
DS
Hoon
L J
LJ
Foshag
J A
JA
Nizze
E
E
Famatiga
E
E
Okun
D L
DL
Morton
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007111:Immunity, Cellular; D007167:Immunotherapy; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D008875:Middle Aged; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014612:Vaccines / Q000276:immunology*
D015234:HLA-A Antigens; D014612:Vaccines