Growth inhibition of tumour cells by a liposome-encapsulated, mycolic acid-containing glycolipid, trehalose 2,3,6'-trimycolate.
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.
Ohtsubo
Y
Y
Osaka Research Institute, Sawai Pharmaceutical Co., Ltd., Japan.
Furukawa
M
M
Imagawa
T
T
Sugimoto
N
N
Ikutoh
M
M
Nakatsugi
S
S
Katoh
Y
Y
Shinka
S
S
Dohi
Y
Y
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004337:Drug Carriers; D006017:Glycolipids / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D008081:Liposomes; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D012515:Mast-Cell Sarcoma / Q000628:therapy; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*
D016207:Cytokines; D004337:Drug Carriers; D006017:Glycolipids; D008081:Liposomes; C060019:trehalose 2,3,6'-trimycolate