Lethal toxicity and adjuvant activities of synthetic TDM and its related compounds in mice.
Trehalose-6,6'-dimycolate (TDM) and its monosaccharide-type analogues were synthesized, and their lethal and adjuvant activities were examined in mice. All the monosaccharide-type analogues with a glucose or N-acetylglucosamine moiety were devoid of lethal toxicity to mice; in particular, D-GlcNAcM(1-deoxy) and D-GlcNM did not cause any loss of body weight at an early stage after intravenous administration as a 9% oil-in-water emulsion. Intraperitoneal administration of D-GlcNAcM(1-deoxy) in aqueous suspension, as well as TDM, could activate macrophages to become tumoricidal against tumour cells, whereas D-GlcNAcM(1-deoxy) in oil emulsion, unlike TDM, caused no granulomatous formation in the lung after intravenous injection. Squalane-treated D-GlcNAcM(1-deoxy) showed significant inhibition of spontaneous lung metastases by B16-BL6 melanoma cells when it was administered twice intratumorally. The non-toxic monosaccharide-type analogue of TDM [D-GlcNAcM(1-deoxy)] was a beneficial adjuvant for the activation of macrophages and the prevention of cancer metastasis.
Sakurai
T
T
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Saiki
I
I
Ishida
H
H
Takeda
K
K
Azuma
I
I
D000276:Adjuvants, Immunologic; D000818:Animals; D003311:Cord Factors / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D006017:Glycolipids / Q000633:toxicity*; D006099:Granuloma / Q000517:prevention & control; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL
D000276:Adjuvants, Immunologic; D003311:Cord Factors; D006017:Glycolipids