Activation by synthetic lipid A subunit analogues (GLA compounds) of tumoricidal properties in human blood monocytes.
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.
Maeda
H
H
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Saiki
I
I
Yamamoto
N
N
Takahashi
T
T
Sekiguchi
S
S
Kiso
M
M
Hasegawa
A
A
Azuma
I
I
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology
D000276:Adjuvants, Immunologic; D008050:Lipid A; D008070:Lipopolysaccharides; C056260:GLA 60