Active immunotherapy as an adjunct to chemotherapy in the treatment of disseminated malignant melanoma: a pilot study

Abstract

In patients with disseminated malignant melanoma an optimal method of immunization with irradiated tumour cells was developed by reference to an in vitro assay for circulating specific serum inhibitors of cell mediated cytotoxicity. This immunization protocol consisted of the intradermal inoculation of 2 times 10(7) irradiated allogeneic melanoma cells admixed with 50 mug of percutaneous BCG. This method of immunization induced a significant but transient fall in the specific inhibitory effects of the sera on tumour directed cytotoxic activity of the patients' lymphocytes. In a pilot group of 30 patients with disseminated malignant melanoma being treated with chemotherapy (DTIC and vincristine) the immunotherapy was given midway between courses of the cytotoxic drugs. There was a correlation between the effects on circulating inhibitor and clinical outcome. The number of objective regressions occurring in this small pilot group was surprisingly high (17/30) and these clinical effects, although obtained in a series without concurrent controls, are presented for discussion. We suggest that the approach illustrated by this study, employing in vitro assays of tumour directed immune responses, may provide a suitable rational basis for the use of active immunotherapy as an adjunct to chemotherapy in the treatment of malignant disease.

Clinical trial of combination chemotherapy and specific active immunotherapy in disseminated melanoma

“…However, when their series is analysed by the tissue sites which responded to the therapy, 12/17 of the responses were in skin and lymph node and only 5 in visceral deposits. The similarity in the pattern of responses in both groups in this study and in Currie and McElwain's (1975) series implies that the major active agent in both protocols is the chemotherapy (probably mainly DTIC). As suggested above, the immunotherapy used may play a minor role by increasing the response of certain sites to chemotherapy, but it has not altered the survival rate.…”

“…The results show that the responses in the combined groups C and (C + I) of 36% is lower thain the 57% response rate reported by Currie and McElwain (1975). Their group of patients were treated with DTIC (at the same dosage as used here) plus vincristine and all their patients received immunotherapy with melanoma cells plus BCCG.…”

“…Immunization of melanoma patients with their own irradiated tumour cells has been shown to stimulate both cytotoxic antibody (Ikonopisov et al, 1970) and cytotoxic lymphocytes (Currie, Lejeune and Fairley, 1971). More recent studies have reported that both the combination of chemotherapy with non-specific immunotherapy (Gutterman et al, 1973) and specific active immunotherapy with allogeneic melanoma cells (Currie and McElwain, 1975) can improve the response rates in malignant melanoma. In this study the specific active immunotherapy was based on the work of Currie and McElwain (1975).…”

“…More recent studies have reported that both the combination of chemotherapy with non-specific immunotherapy (Gutterman et al, 1973) and specific active immunotherapy with allogeneic melanoma cells (Currie and McElwain, 1975) can improve the response rates in malignant melanoma. In this study the specific active immunotherapy was based on the work of Currie and McElwain (1975).…”

In vivo evaluation of cell mediated immunity against human melanoma

“…Occasional cases of spontaneous regression [4,10,11,27], histological findings at the tumor sites [7,21], and delayed cutaneous hypersensitivity reactions [3,12] suggest an immunological relationship between the tumor and host. Various forms of immunotherapy including nonspecific active [23,30], specific active [6,17,35], adoptive specific [25,31], and passive specific treatments [13,40] have been performed in an attempt to increase the efficacy of the host antitumor immune response. We have utilized specific active immunotherapy involving serial injections of X-irradiated, neur-aminidase treated melanoma cells admixed with BCG in a large group of patients [32].…”