Abstract |
We investigated the therapeutic effects of ONO-4007, a novel synthetic lipid A derivative with low toxic activities, on transplanted hepatocellular carcinoma KDH-8 in WKAH rats. ONO-4007 brought about complete cures in about 60% of rats bearing tumor necrosis factor ( TNF)-alpha-sensitive KDH-8 cells, whereas no complete cure was observed in rats bearing cKDH-8/11 which is identical to KDH-8 but a TNF-alpha-resistant cell line, KMT-17 and KEG-1. Then we examined the influence of rabbit anti- TNF-alpha antibody on the therapeutic effects of ONO-4007 against the TNF-alpha-sensitive KDH-8. The concomitant administration of the rabbit anti- TNF-alpha antibody completely abrogated the therapeutic effects of ONO-4007. On the other hand, rechallenged tumor cells of both KDH-8 and cKDH-8/11 were completely rejected in the rats cured of KDH-8 tumor, although no rejection of KEG-1 was observed. Moreover, Winn assay, i.e. the tumor cell neutralizing assay, indicated that CD4+ T cells were involved in the antigen-specific transplantation resistance. These findings suggest that antigen-specific T cell responses are involved in the complete cure of tumors after the treatment with ONO-4007, although its therapeutic effect is initiated by TNF-alpha.
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Authors | K Matsushita, M Kobayashi, Y Totsuka, M Hosokawa |
Journal | Anti-cancer drugs
(Anticancer Drugs)
Vol. 9
Issue 3
Pg. 273-82
(Mar 1998)
ISSN: 0959-4973 [Print] England |
PMID | 9625438
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies
- Antineoplastic Agents
- Interleukin-1
- Lipid A
- ONO 4007
- Tumor Necrosis Factor-alpha
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Topics |
- Animals
- Antibodies
(pharmacology)
- Antineoplastic Agents
(therapeutic use, toxicity)
- CD4-Positive T-Lymphocytes
(drug effects, immunology)
- CD8-Positive T-Lymphocytes
(drug effects, immunology)
- Cell Division
- Female
- Humans
- Interleukin-1
(biosynthesis)
- Lipid A
(analogs & derivatives, therapeutic use, toxicity)
- Liver Neoplasms, Experimental
(drug therapy, immunology, pathology)
- Rabbits
- Rats
- Rats, Wistar
- Spleen
(immunology)
- Tumor Necrosis Factor-alpha
(biosynthesis, immunology)
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