The antitumor effects of levamisole in mice are mediated by NC-1.1+ cells |
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Authors: | Gregory R Clarke Robert C Burton Y Cheng Smart |
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Institution: | (1) Discipline of Surgical Science, Faculty of Medicine and Health Sciences, University of Newcastle, N.S.W. 2308, Australia, AU;(2) Anti-Cancer Council of Victoria, Melbourne, Victoria 3053, Australia, AU;(3) Discipline of Surgical Science, Faculty of Medicine and Health Sciences, Level 4 David Maddison Building, Royal Newcastle Hospital, Newcastle, N.S.W. 2300, Australia Tel. +61 49 236168; Fax +61 49 236984 e-mail: mdycs@mail.newcastle.edu.au, AU |
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Abstract: | Murine natural cytotoxicity, which is a major component of the innate immune response in cancer, is mediated by leukocytes
that express the NC-1.1 receptor. Mice depleted of natural cytotoxicity by treatment with an anti-NC-l.1 mAb show enhanced
growth of certain transplantable tumors, so agents that enhance natural cytotoxicity by NC-1.1+ cells have the potential to be effective anticancer therapeutic agents. We have examined the immunomodulatory effect of levamisole
on natural cytotoxicity mediated by NC-1.1+ cells against the BALB/c WEHI-164 murine fibrosarcoma. Administration of levamisole to BALB/c mice significantly enhanced
in vitro splenic natural cytotoxicity against 51Cr-labeled WEHI-164 tumor cells. The effect was most marked 48 h after levamisole treatment, at a dose of 10 mg/kg body weight.
This enhancement of natural cytotoxicity by levamisole could be completely abrogated by pretreatment of mice with an anti-NC-1.1
mAb. Treatment of BALB/c mice with 10 mg/kg levamisole significantly reduced the growth of WEHI-164 and this effect was abrogated
by pretreatment of mice with anti-NC-1.1, indicating that the antitumor effect of levamisole was mediated, at least in part,
via NC-1.1+ cells.
Received: 5 June 1997 / Accepted: 31 July 1997 |
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Keywords: | Levamisole Natural cytotoxicity NC-1 1+ cells Tumor surveillance |
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