Restoration of immune responses in tumor-bearing mice by ONO-4007, an antitumor lipid A derivative.
ONO-4007, a synthetic lipid A derivative, has been found to exhibit potent antitumor activity in several animal models. In the present study, we examined the effects of ONO-4007 on delayed-type hypersensitivity (DTH) reaction and antibody production in Meth A sarcoma-bearing BALB/c mice. The DTH reaction to sheep red blood cells (SRBC) and the IgG production against keyhole limpet hemocyanin (KLH), were depressed in tumor-bearing mice as well as in normal mice given Mitomycin C (MMC). However, ONO-4007 restored these immune responses to normal levels. In addition, in vitro studies showed that ONO-4007 induced the production of tumor necrosis factor-alpha (TNF-alpha) in splenic adherent cells of tumor-bearing mice more than those in normal mice. Though ONO-4007 alone had little effect on the induction of IL-2 production in spleen cells, it augmented the Concanavalin A (Con A)-stimulated IL-2 production. Moreover, ONO-4007 had a mitogenic effect on spleen cells. These results suggest that ONO-4007 may improve immunocompetence in tumor-bearing hosts and contribute to the induction of antitumor immunity and prevention of bacterial infections.
Matsumoto
N
N
Fukui Research Institute, Ono Pharmaceutical Co. Ltd., Japan.
Aze
Y
Y
Akimoto
A
A
Fujita
T
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000502:physiology; D004912:Erythrocytes / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D012756:Sheep; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D007376:Interleukin-2; D008050:Lipid A; D008934:Mitogens; C086889:ONO 4007; D014409:Tumor Necrosis Factor-alpha; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin