Treatment of metastatic melanoma with an autologous tumor-cell vaccine: clinical and immunologic results in 64 patients.
We treated 64 patients with metastatic melanoma using a melanoma vaccine preceded by low-dose cyclophosphamide (CY), and monitored immunologic effects and antitumor activity. On day 0, the patients were given CY 300 mg/m2 intravenously. Three days later, they were injected intradermally with vaccine consisting of 10 to 25 x 10(6) autologous, enzymatically dissociated, cryopreserved, irradiated (25 Gy) tumor cells mixed with bacillus Calmette-Guérin (BCG). This treatment sequence was repeated every 28 days. Of 40 assessable patients with measurable metastases, five had responses, four complete and one partial, with a median duration of 10 months (7 to 84+ months). In six additional patients, we observed an antitumor response that seems to be peculiar to this vaccine therapy: the regression of metastatic lesions that appeared after the immunotherapy was begun. Delayed-type hypersensitivity (DTH) to autologous, mechanically dissociated melanoma cells that had not been exposed to extraneous antigens, such as enzymes or fetal calf serum, increased significantly following immunotherapy (day 0 v day 49, P less than .001; day 0 v day 161, P less than .001; day 0 v day 217, P = .021). Antitumor responses to the vaccine were strongly associated with DTH, as indicated by three observations: (1) eight of 10 patients who exhibited tumor regression had positive DTH, (2) in postsurgical adjuvant patients, there was a highly significant linear relationship (P less than .001) between the intensity of DTH to autologous melanoma cells and the time to recurrence of tumor, and (3) nine patients who developed DTH to the autologous melanoma cells in their original vaccine developed new metastases that failed to elicit DTH or elicited a much smaller response. In three cases, we were able to excise regressing tumors for histologic examination; such tumors were characterized by an intense infiltration of lymphocytes. This demonstration that an immune response to melanoma-associated antigens can be elicited in cancer-bearing patients provides some basis for optimism about the prospects for developing active immunotherapy that has practical therapeutic value.
Berd
D
D
Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107.
Maguire
H C
HC
McCue
P
P
Mastrangelo
M J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007111:Immunity, Cellular; D016233:Immunotherapy, Active / Q000009:adverse effects / Q000379:methods*; D007262:Infusions, Intravenous; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis
D001500:BCG Vaccine; D003520:Cyclophosphamide