cord-factors and Remission--Spontaneous

The influence of mineral oil, squalane, squalene, or peanut oil on the antitumor activity of emulsified Bacillus Calmette-Guérin cell walls or emulsified trehalose-6,6'-dimycolate was studied in mice, each with an established transplant of a syngeneic fibrosarcoma. Each animal received an intratumoral injection of Bacillus Calmette-Guérin cell walls (0.6 mg/mouse) or trehalose-6,6'-dimycolate (0.1 mg/mouse) emulsified in 1 to 10% oil. Emulsions of squalene or squalane but not peanut oil were effective substitutes for mineral oil as carriers of Bacillus Calmette-Guérin cell walls in the treatment of the tumor. Trehalose-6,6'-dimycolate was therapeutically active when it was incorporated in any of these four oils. The number of animals in which tumor regressed completely depended on the concentration of oil in the emulsion.

Topics: Animals; Arachis; BCG Vaccine; Cell Wall; Cord Factors; Glycolipids; Male; Mice; Mineral Oil; Oils; Remission, Spontaneous; Sarcoma, Experimental; Squalene

The clinical efficacy of intralesional immunotherapy utilizing Mycobacterium smegmatis cell wall skeleton (CWS) and trehalose dimycolate attached to oil droplets was investigated in 15 patients with advanced malignant melanoma. Patients received 300 microgram to 1050 microgram of the CWS combined with one-half that amount of trehalose dimycolate every 1 to 2 weeks for a total of 8 treatments. Therapy was continued if regression of injected lesions only occurred. Therapy was discontinued if regression of noninjected disease also occurred. Six of the 15 patients had regression of at least one injected lesion. Four of these 6 patients also had regression of noninjected disease lasting 4+, 6, 16 and 18+ months. Response was highly related to immune status. Six (83%) of 7 patients who reacted to one of a battery of skin tests responded. All 8 patients who did not react to skin tests failed to respond to therapy. There was no correlation of response with sex, prior therapy, disease-free interval or presence of visceral disease. Mycobacterial CWS and trehalose dimycolate is an effective immunotherapeutic agent. Additional studies of purified immunoadjuvants are warranted.

Topics: Cell Wall; Cord Factors; Female; Glycolipids; Humans; Immunity; Immunotherapy; Male; Melanoma; Mycobacterium; Remission, Spontaneous; Skin Neoplasms

Injection of emulsified 6,6'-di-O-2-tetradecyl-3-hydroxyoctadecanoyl-a, a trehalose designated C76, a synthetic analogue of the mycobacterial glycolipid trehalose-6,6'-dimycolate (TDM), into transplants of an established, syngeneic murine fibrosarcoma induced complete regression of tumor in a number of animals. The number of animals in which tumor regressed completely dependent on the amount of oil in the emulsion. On a weight basis, C76 was at least as active as TDM. Intralesional injection of an emulsified mixture of C76 and endotoxin (ET) or of TDM and ET caused regression of an established transplant of a guinea-pig hepatoma in syngeneic animals. In mice, intravenously administered emulsions of C76 were less toxic and less granulomagenic than those made with TDM.

Topics: Animals; Cell Line; Cord Factors; Disaccharides; Drug Evaluation, Preclinical; Emulsions; Fibrosarcoma; Glycolipids; Guinea Pigs; Injections; Injections, Intravenous; Male; Mice; Neoplasm Transplantation; Remission, Spontaneous; Sarcoma, Experimental; Transplantation, Isogeneic; Trehalose