The antitumor effects of levamisole in mice are mediated by NC-1.1+ cells.
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.
Clarke
G R
GR
Discipline of Surgical Science, Faculty of Medicine and Health Sciences, University of Newcastle, N.S.W., Australia.
Burton
R C
RC
Smart
Y C
YC
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D007978:Levamisole / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology; D011506:Proteins / Q000032:analysis*
D000276:Adjuvants, Immunologic; D011506:Proteins; D007978:Levamisole