RRC ID 38964
Author Matsumoto N, Aze Y, Akimoto A, Fujita T.
Title Restoration of immune responses in tumor-bearing mice by ONO-4007, an antitumor lipid A derivative.
Journal Immunopharmacology
Abstract 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.
Volume 36(1)
Pages 69-78
Published 1997-4
DOI 10.1016/s0162-3109(96)00161-0
PII S0162310996001610
PMID 9129998
MeSH Adjuvants, Immunologic / pharmacology* Animals Antineoplastic Agents / pharmacology* Cell Adhesion / physiology Erythrocytes / immunology Hemocyanins / immunology Hypersensitivity, Delayed / immunology Immunoglobulin G / biosynthesis Interleukin-2 / biosynthesis Lipid A / analogs & derivatives* Lipid A / pharmacology Lymphocyte Activation / drug effects Male Mice Mice, Inbred BALB C Mitogens / pharmacology Sarcoma, Experimental / drug therapy* Sarcoma, Experimental / immunology* Sarcoma, Experimental / metabolism Sheep Spleen / drug effects Spleen / immunology Spleen / metabolism Tumor Necrosis Factor-alpha / biosynthesis
Times Cited 10
Human and Animal Cells