Activation by synthetic lipid A subunit analogues (GLA compounds) of tumoricidal properties in human blood monocytes

Abstract

The authors have determined that synthetic lipid A subunit analogues (GLA compounds), as well as E. coli type lipopolysaccharide (LPS) and synthetic lipid A (compound 506), are able to stimulate human monocytes to become cytotoxic against tumour target cells in vitro. GLA-60, a synthetic lipid A subunit analogue of low toxicity, was found to be more active for the induction of tumoricidal monocytes than GLA-59, and similar to that of LPS. GLA-60 could induce not only the secretion of cytotoxic factor into the culture supernatant but also expression of the membrane-associated form of cytotoxic factor in human monocytes. Supernatant-mediated cytotoxicity was completely inhibited by the addition of monoclonal anti-human TNF antibody. These results indicate that a synthetic lipid A subunit analogue, GLA-60, would be a useful activator of tumoricidal monocytes in spite of its low toxicity.