Active-specific immunotherapy for melanoma.
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.
Mitchell
M S
MS
Department of Medicine, University of Southern California School of Medicine, Los Angeles.
Harel
W
W
Kempf
R A
RA
Hu
E
E
Kan-Mitchell
J
J
Boswell
W D
WD
Dean
G
G
Stevenson
L
L
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D000951:Antigens, Neoplasm / Q000032:analysis; D017358:Cell Wall Skeleton; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007167:Immunotherapy; D007958:Leukocyte Count; D008050:Lipid A / Q000031:analogs & derivatives / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D009088:Mucoproteins / Q000627:therapeutic use; D009171:Mycolic Acids / Q000627:therapeutic use; D012074:Remission Induction; D012878:Skin Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy; D012882:Skin Tests; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D017358:Cell Wall Skeleton; D008050:Lipid A; D009088:Mucoproteins; D009171:Mycolic Acids; C048436:monophosphoryl lipid A