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Published on: August 23, 2019
The antitumor effects of levamisole in mice are mediated by NC-1.1+ cells
G R Clarke1, R C Burton, Y C Smart
1Discipline of Surgical Science, Faculty of Medicine and Health Sciences, University of Newcastle, N.S.W., Australia.
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-1.1 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.
Insights
Levamisole enhances natural cytotoxicity in mice, a key part of the immune response against cancer. This immune boost, mediated by NC-1.1+ cells, significantly reduces tumor growth, offering potential as an anticancer therapy.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Murine natural cytotoxicity, mediated by NC-1.1+ leukocytes, is crucial for innate immune response in cancer.
- Depletion of natural cytotoxicity leads to enhanced tumor growth, highlighting the therapeutic potential of agents that boost NC-1.1+ cell activity.
Purpose of the Study:
- To investigate the immunomodulatory effects of levamisole on natural cytotoxicity mediated by NC-1.1+ cells.
- To assess levamisole's efficacy against the BALB/c WEHI-164 murine fibrosarcoma.
Main Methods:
- Administration of levamisole to BALB/c mice.
- In vitro assessment of splenic natural cytotoxicity against 51Cr-labeled WEHI-164 tumor cells.
- Abrogation of levamisole's effects using anti-NC-1.1 monoclonal antibody (mAb).
- Evaluation of WEHI-164 tumor growth in levamisole-treated mice.
Main Results:
- Levamisole significantly enhanced in vitro splenic natural cytotoxicity against WEHI-164 cells, peaking at 48 hours post-treatment (10 mg/kg).
- The enhancement of natural cytotoxicity by levamisole was completely blocked by pretreatment with anti-NC-1.1 mAb.
- Levamisole treatment (10 mg/kg) significantly reduced WEHI-164 tumor growth.
- The antitumor effect of levamisole was abrogated by anti-NC-1.1 mAb pretreatment, indicating mediation via NC-1.1+ cells.
Conclusions:
- Levamisole effectively enhances natural cytotoxicity mediated by NC-1.1+ cells.
- The antitumor effects of levamisole against WEHI-164 fibrosarcoma are, at least partly, dependent on NC-1.1+ cell activity.
- Levamisole demonstrates potential as an anticancer therapeutic agent by modulating innate immunity.
