Twenty-five patients with metastatic melanoma were treated with a therapeutic 
vaccine ("theraccine") consisting of allogeneic melanoma lysates and a novel 
adjuvant, DETOX (Ribi ImmunoChem Research, Inc, Hamilton, MT). Each patient 
received 200 antigenic units (20 x 10(6) tumor cell equivalents) subcutaneously 
on weeks 1, 2, 3, 4, and 6. Clinical responses included one complete remission, 
three partial remissions, and a long-term (17-month) stability. Two other 
patients had mixed responses, with partial remissions of numerous subcutaneous 
nodules. Sites of responsive disease included primarily the skin, but ileal, 
breast, and a liver metastasis also responded. Removal of residual lesions in 
patients with partial remissions, whose other lesions had disappeared during 
treatment, led to long disease-free survivals. The median duration of remission 
was 17 months, with four of the five responders alive for at least 24 months 
after treatment. An increase in precursors of cytolytic T cells (CTLs) 
correlated with clinical outcome, when complete, partial, and mixed responses 
and long-term stability were considered. The CTLs recognized melanoma-associated 
antigens on many cell lines, but not other types of tumor or normal lymphocytes. 
Skin-test reactivity to melanoma antigens and serum antibodies against the 
melanoma cells was unrelated to clinical response. Toxicity was minimal, 
restricted largely to minor soreness at the site of injection. Only five 
patients, four of whom were treated with repeated courses, developed severe 
granulomas. These results confirm that active-specific immunization with 
allogeneic lysates of melanoma administered with the adjuvant DETOX can induce 
immunity to melanoma, and can induce regressions of disease in a proportion of 
patients with metastatic disease with little toxicity.