Intravenous, intralesional and endolymphatic administration of lymphokines in human cancer.

Starting in 1976 we have given two types of lymphokine preparation to 78 individual patients with cancer with no evidence of long-term toxicity. Lymphokine from the 1788 lymphoblastoid line (1788-LK) was given intravenously and intralesionally to 39 of these patients and buffy coat interleukin (BC-IL) to 40 of the patients. On intravenous injection both preparations produced pyrexia and other acute phase changes but with an earlier time course after BC-IL. Feelings of well-being were volunteered and the patients often remained in a steady clinical state for a long time when previously their condition had been deteriorating. Histological studies after intralesional injection into recurrent breast nodules (1788-LK and BC-IL) and prostate (1788-LK) showed an inflammatory cell infiltrate and tumour cell necrosis. Endolymphatic infusion of BC-IL in 23 patients with malignant melanoma was followed by clinical, radiological and histological evidence of lymph node activation. 10 of these patients had had excision of poor prognosis primary tumour only and during the follow-up period (5-17 months) none had a recurrence. Our experience suggests that administration of lymphokines has a place in the total management of cancer patients.

Histological features of skin reactions to human lymphoid cell line lymphokine in patients with advanced cancer.

Lymphokines (LCL-LK) prepared from the human lymphoid cell line RPMI 1788 were injected intradermally into tumour-bearing patients. Biopsies of skin reactions were obtained for histological study from 30 min. to 72 hr, and for comparison, biopsies were taken at similar times of tuberculin reactions in tuberculin-positive patients. The early response to LCL-LK consisted of polymorph adherence to vascular endothelium (at 30 min.) followed by polymorph exudation, oedema and haemorrhage (1-2 hr); mononuclear and eosinophilic leucocyte emigration began at 4 hr; and by 12 hr, when the reaction was maximal clinically, there was widespread pleomorphic leucocytic infiltration of the dermis. At later times (48-72 hr) skin reactions to LCL-LK showed predominantly mononuclear cell infiltration and hypertrophy of vascular endothelium. Electron microscopy at 48 hr revealed perivascular lymphocytes and macrophages. The skin reaction to LCL-LK appeared to superimpose an early component of marked polymorph infiltration, oedema and haemorrhage upon a mononuclear cell exudation similar to that seen in the tuberculin reaction. It was concluded that the later phase of the skin reaction to lymphoid cell line lymphokine in the human bore a close histological similarity to the established tuberculin reaction. The LCL-LK reaction occurred in patients anergic to recall antigens. Its intensity was mainly related to dose and did not vary substantially between different batches of lymphokines.

Changes induced by local injection of human lymphoid cell lymphokine into dermal metastases of breast carcinoma: a light and electron microscopical study.

Lymphokines (LCL-LK) prepared from the human lymphoid cell line RPMI 1788 were injected into dermal nodular metastases of three patients with advanced breast carcinoma anergic to recall antigen (tuberculin). Three different injection schedules were employed. Ten such nodules were examined by excision biopsy and their histological appearances were compared with biopsies of four further nodules not injected with the lymphokine. Intranodular injection of LCL-LK resulted in clinical regression of tumour and histological evidence of tumour-cell necrosis with pleomorphic leucocytic infiltration by polymorphs, macrophages and lymphocytes. Electron microscopy of two such nodules failed to show close cell contact between leucocytes and tumour cells prior to tumour-cell necrosis. This study extends evidence that injection of inflammatory lymphokines into accessible tumour can result in local tumour regression and it suggests that such tumour-cell destruction may be the result of a variety of factors operating during local inflammatory response.