Induction of cell-mediated immunity to autologous melanoma cells and regression of metastases after treatment with a melanoma cell vaccine preceded by cyclophosphamide.
There is considerable evidence in animal tumor systems that antitumor immunity is modulated by suppressor T-lymphocytes, and that the cytotoxic drug cyclophosphamide (CY) can abrogate that suppression. We measured the acquisition of delayed-type hypersensitivity (DTH) to autologous melanoma cells in 19 patients with metastatic malignant melanoma. The patients were treated with an autologous melanoma cell vaccine, either given alone, or given 3 days after the administration of CY, 300 mg/m2 i.v. The DTH responses of CY-pretreated patients were significantly greater than those of control (vaccine only) patients. Thus, after two vaccine treatments, the median DTH responses (mm induration) were as follows: controls, 4 mm; CY pretreated, 11 mm; P = 0.034, Mann-Whitney U test, 2-tailed. Whereas seven of eight CY-pretreated patients developed DTH to autologous melanoma cells of at least 5 mm, only two of seven controls did so (P = 0.034, Fisher's exact test). Two patients had significant antitumor responses to treatment with CY plus vaccine, consisting of complete disappearance of skin metastases and a pulmonary nodule in one, and regression of s.c. and liver metastases in the other. Both patients remain free of melanoma after 42 and 33 mo, respectively.
D
D
Berd
H C
HC
Maguire
M J
MJ
Mastrangelo
D000328:Adult; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007167:Immunotherapy; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D014612:Vaccines / Q000276:immunology
D014612:Vaccines; D003520:Cyclophosphamide