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KMID : 0357319940290020231
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Journal of the Korean Society for Microbiology
1994 Volume.29 No. 2 p.231 ~ p.244
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Antitumor Effect of Monophosphoryl Lipid A, Polyadenylic-Polyuridylic Acid and Cisplatin on B16 Melanoma-indued Pulmonary Metastasis in Mice.
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조철호
이봉기/주민경/김성규/김주덕
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Abstract
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Despite aggressive surgery, radiation, and combined chemotherapy, recurrence after treat ment of primary cancer is common. Complete eradication of cancer cells with these modalities is hard, if at all, to achieve.
Immunity is usually depressed in hosts with tumor and a strong relationship exists between immunocompetence and prognosis of cancer. Immunotherapy thus aims at stimulating natural host defense mechanism to facilitate tumor regression.
Augmentation
of
natural killer(NK) cell cytotoxicity, macrophage activation, and interferon(IFN) -(-mediated T lymphocyte proliferation are believed to be the main antitumor effects of immunotherapy.
Monophosphoryl lipid A(MPL), a derivative of lipopolysaccharide(LPS), which has antitumor activity with low toxicity, has been shown to enhance antibody production with increased INF-( in both young adult and aging mice. Poyadenylic-poyuridylie
acid
[poly(A) ( poly(U)] is a nontoxic and metabolically stable immunomodulator, capable of efficiently stimulating various compartments of host-immune system, thereby enhancing their antitumor activity. It has been successfully used in adjunct
treatment of
human breast and stomach cancer, increasing patient survival and decreasing recurrence. This study looked into antitumor effects of MPL, poly(A) ( poly(U) and cisplatin, used alone or in combination, against B16 melanoma lung metastasis in mice,
and the
following results were obtained:
1. Antitumor effects of MPL, poly(A) ( poly(U) and cisplatin were significantly higher in the mice treated with these agents than the saline-treated controls.
2. The combined use of MPL and poly(A) ( poly(U) tended to show, though not significant, higher antitumor effect than the sole use of either MPL or poly(A) ( poly(U) in mice not previously treated with cisplatin, but not in mice pretreated with
cisplatin.
3. In vivo inoculation of MPL and poly(A) ( poly(U) significantly enhanced cytotoxicity of spleen cells against both YAC-1 cells and B16 melanoma cells, but enhanced cytotoxicity of peritoneal macrophages only against the former(YAC-1 cells). In
vitro,
it failed to increase cytotoxicity of either spleen cells or peritoneal macrophages.
4. IL-2 and IFN-( production Were signicautly higher in the mice treated with MPL or poly(A) poly(U) than the controls with the production in the mice treated with MPL higher than with poly(A)oly(U). IL-4 production was not different between the
mice
treated with poly(A) ( poly(U) and the controls, but in the MPL-treated mice, it was significantly lower than in the controls.
Antitumor activity of MPL and poly(A) ( poly(U) against metastatic lung cancer appears to arise from increased cytotoxicity of NK cells and macrophages, mediated by the increased IL-2 and IFN-( production. In particular compared with poly(A) (
poly(U),
MPL, the substance showing as in this study a high antitumor effect and significantly increased production of IL-2 and INF-(, the cytokines believed to be important in cell-mediated immunity, appears promising as a potentially useful
immunotherapeutic
agent.
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KEYWORD
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