MALTOSE TETRAPALMITATE, A NONTOXIC IMMUNOPOTENTIATOR WITH ANTI-TUMOR ACTIVITY

Abstract

The attempt to synthesize a lipid A-like component (the active portion of lipopolysaccharides, but lacking its endotoxic activity) resulted in the production of fatty acyl sugars of which maltose tetrapalmitate yielded the most promising results. It showed no endotoxic activity and elicited an antitumor response in tumor-transplanted animals as shown by an enhancement of the host''s capacity to reject a large number of tumor cells, retardation of growth in tumor size and induction of hemorrhagic necrosis in certain tumors. Experiments with [rat 13762] mammary ascites carcinoma show maltose tetrapalmitate to be as effective as bacterial glycolipid mR595 in its antitumor activity. The degree of sensitivity to maltose tetrapalmitate varied with the tumor-host system: mammary ascites carcinoma < NH [rat Novikoff heptoma] = Cl2TSV5S [nude mouse] = B-16 [mouse melanoma] < L-26 [mouse colon tumor]. The mode of action of maltose tetrapalmitate appeared to be via its modulation of the immune system. It was itself noncytotoxic to tumor cells in vitro. It stimulated the spleen cells of certain animals mitogenically, although it caused tumor rejection in all the types of animals tested. It activated peritoneal exudate macrophages in tumor-bearing animals; whether specifically or nonspecifically was not established.