Abstract
In vivo growth of syngeneic tumour cells in the peritoneal cavity was strongly inhibited by intraperitoneal injection of a liposome-encapsulated, mycolic acid-containing glycolipid, trehalose 2,3,6'-trimycolate (TTM), derived from a non-pathogenic, acid-fast bacterium. Gordona aurantiaca. Peritoneal macrophages from mice after this treatment lysed tumour cells in vitro at a low effector/target ratio, and their culture supernatant inhibited tumour cell growth. The supernatant inhibited growth of not only tumour necrosis factor (TNF)-sensitive tumour cells, but also TNF-insensitive tumour cells. This inhibitory activity was enhanced by addition of lipopolysaccharide (LPS) to the culture medium of the macrophages. The macrophages released more superoxide (O2-), TNF and interleukin-1 (IL-1) on LPS triggering, and the releases of these compounds were further increased by addition of recombinant interferon-gamma (IFN-gamma) to the medium. Moreover, splenic T cells of TTM liposome-primed mice were found to produce eight times more IFN-gamma upon stimulation with LPS. These results indicated that priming with TTM liposomes resulted in strong activation of macrophages, which lysed tumour cells directly and also inhibited tumour cell growth by released factors.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Armstrong J. A. Cytopathic effect inhibition assay for interferon: microculture plate assay. Methods Enzymol. 1981;78(Pt A):381–387. doi: 10.1016/0076-6879(81)78145-x. [DOI] [PubMed] [Google Scholar]
- Bangham A. D., Standish M. M., Watkins J. C. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 1965 Aug;13(1):238–252. doi: 10.1016/s0022-2836(65)80093-6. [DOI] [PubMed] [Google Scholar]
- Bekierkunst A., Levij I. S., Yarkoni E. Suppression of urethan-induced lung adenomas in mice treated with trehalose-6,6-dimycolate (cord factor) and living bacillus Calmette Guérin. Science. 1971 Dec 17;174(4015):1240–1242. doi: 10.1126/science.174.4015.1240. [DOI] [PubMed] [Google Scholar]
- Blanchard D. K., Djeu J. Y., Klein T. W., Friedman H., Stewart W. E., 2nd Interferon-gamma induction by lipopolysaccharide: dependence on interleukin 2 and macrophages. J Immunol. 1986 Feb 1;136(3):963–970. [PubMed] [Google Scholar]
- Flick D. A., Gifford G. E. Comparison of in vitro cell cytotoxic assays for tumor necrosis factor. J Immunol Methods. 1984 Mar 30;68(1-2):167–175. doi: 10.1016/0022-1759(84)90147-9. [DOI] [PubMed] [Google Scholar]
- Furukawa M., Ohtsubo Y., Sugimoto N., Katoh Y., Dohi Y. Induction of tumoricidal activated macrophages by a liposome-encapsulated glycolipid, trehalose 2,3,6'-trimycolate from Gordona aurantiaca. FEMS Microbiol Immunol. 1990 Sep;2(2):83–88. doi: 10.1111/j.1574-6968.1990.tb03504.x. [DOI] [PubMed] [Google Scholar]
- Grand-Perret T., Lepoivre M., Petit J. F., Lemaire G. Macrophage activation by trehalose dimycolate requirement for an expression signal in vitro for antitumoral activity; biochemical markers distinguishing primed and fully activated macrophages. Eur J Immunol. 1986 Apr;16(4):332–338. doi: 10.1002/eji.1830160403. [DOI] [PubMed] [Google Scholar]
- Kirchner H., Muchmore A. V., Chused T. M., Holden H. T., Herberman R. B. Inhibition of proliferation of lymphoma cells and T lymphocytes by suppressor cells from spleens of tumor-bearing mice. J Immunol. 1975 Jan;114(1 Pt 1):206–210. [PubMed] [Google Scholar]
- Kohya H., Ishii F., Takano S., Katori T., Ebina T., Ishida N. Antitumor effect of a synthetic cord factor, 6,6'-di-O-decanoyl-alpha,alpha-trehalose (SS554), in mice. Jpn J Cancer Res. 1986 Jun;77(6):602–609. [PubMed] [Google Scholar]
- Le J., Lin J. X., Henriksen-DeStefano D., Vilcek J. Bacterial lipopolysaccharide-induced interferon-gamma production: roles of interleukin 1 and interleukin 2. J Immunol. 1986 Jun 15;136(12):4525–4530. [PubMed] [Google Scholar]
- Lovett D., Kozan B., Hadam M., Resch K., Gemsa D. Macrophage cytotoxicity: interleukin 1 as a mediator of tumor cytostasis. J Immunol. 1986 Jan;136(1):340–347. [PubMed] [Google Scholar]
- Matsumura H., Nakano M. Endotoxin-induced interferon-gamma production in culture cells derived from BCG-infected C3H/HeJ mice. J Immunol. 1988 Jan 15;140(2):494–500. [PubMed] [Google Scholar]
- Ohtsubo Y., Furukawa M., Fujinobu Y., Sugimoto N., Ikutoh M., Katoh Y., Yano I., Higasa M., Shinka S., Dohi Y. [An immune adjuvant activity of mycolic acid-containing glycolipid, trehalose-2,3,6'-trimycolate, derived from Gordona aurantiaca]. Nihon Saikingaku Zasshi. 1989 Mar;44(2):533–539. doi: 10.3412/jsb.44.533. [DOI] [PubMed] [Google Scholar]
- Ohtsubo Y., Furukawa M., Sugimoto N., Ikutoh M., Katoh Y., Yano I., Shinka S., Dohi Y. [In vitro activation of immune cells by a mycolic acid-containing glycolipid, trehalose-2,3,6'-trimycolate, derived from Gordona aurantiaca]. Nihon Saikingaku Zasshi. 1989 Nov;44(6):797–803. doi: 10.3412/jsb.44.797. [DOI] [PubMed] [Google Scholar]
- Orbach-Arbouys S., Tenu J. P., Petit J. F. Enhancement of in vitro and in vivo antitumor activity by cord factor (6-6'-dimycolate of trehalose) administered suspended in saline. Int Arch Allergy Appl Immunol. 1983;71(1):67–73. doi: 10.1159/000233364. [DOI] [PubMed] [Google Scholar]
- Sumi Y., Kurano S., Kato Y., Sawai H., Tomiyasu I., Kaneda K., Imaizumi S., Yano I. [Strain differences in granuloma formation in mice in response to mycolic acid-containing glycolipids of some species of Nocardia and Rhodococcus]. Nihon Saikingaku Zasshi. 1986 Nov;41(6):797–804. doi: 10.3412/jsb.41.797. [DOI] [PubMed] [Google Scholar]
- Tomiyasu I., Yano I. Separation and analysis of novel polyunsaturated mycolic acids from a psychrophilic, acid-fast bacterium, Gordona aurantiaca. Eur J Biochem. 1984 Feb 15;139(1):173–180. doi: 10.1111/j.1432-1033.1984.tb07991.x. [DOI] [PubMed] [Google Scholar]
- Yarkoni E., Meltzer M. S., Rapp H. J. Tumor regression after intralesional injection of emulsified trehalose-6,6'-dimycolate (cord factor): efficacy increases with oil concentration. Int J Cancer. 1977 Jun 15;19(6):818–821. doi: 10.1002/ijc.2910190612. [DOI] [PubMed] [Google Scholar]
- Yarkoni E., Rapp H. J., Polonsky J., Lederer E. Immunotherapy with an intralesionally administered synthetic cord factor analogue. Int J Cancer. 1978 Nov 15;22(5):564–569. doi: 10.1002/ijc.2910220510. [DOI] [PubMed] [Google Scholar]
