ONO-4007 induces specific anti-tumor immunity mediated by tumor necrosis factor-α

被引：42

作者：

Matsushita, K

Kobayashi, M

Totsuka, Y

Hosokawa, M ^{[1
]}

机构：

[1] Hokkaido Univ, Sch Med, Inst Canc, Pathol Lab, Sapporo, Hokkaido 060, Japan

[2] Hokkaido Univ, Sch Dent, Dept Oral Surg 2, Sapporo, Hokkaido 060, Japan

来源：

ANTI-CANCER DRUGS | 1998年 / 9卷 / 03期

关键词：

CD4 T cell; lipid A; transplantation resistance; tumor necrosis factor-alpha;

D O I：

10.1097/00001813-199803000-00010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. [(C) 1998 Rapid Science Ltd.].

引用

页码：273 / 282

页数：10

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