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Influence of Surgical Removal and Effect of Levamisole on Cytotoxic T-Cell-mediated Antitumor Immunity in Mice

Pharmaceuticals Research Laboratory, Kyowa Hakko Kogyo Co., Ltd., Shimotogari 1188, Nagaizumi-cho, Sunto-gun, Shizuoka 411 [K. G., M. M.], and Medical Institute of Bioregulation, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812 [K. N.], Japan

In BALB/c mice bearing syngeneic fibrosarcoma Meth 1 tumors, effects of surgical removal and levamisole (LMS) on the growth of reinoculated Meth 1 cells were investigated. The growth of secondary tumors in mice with surgical removal of primary tumors was significantly inhibited as compared with that of secondary tumors in primary tumor-bearing mice without surgical removal. LMS (2.5 mg/kg) augmented the growth inhibition of secondary tumors. Its effect was significant only in mice bearing primary tumors without surgical removal.

Cytotoxicity, which was detected in the spleen cells of Meth 1-bearing mice, was mediated by tumor-specific cytotoxic T-cells and augmented after surgical removal of the tumors. LMS augmented the cytotoxicity when it was administered before surgical removal of the tumors but not after surgical removal. The spleen cells of Meth 1-bearing mice in the last stage of tumor development did not exhibit cytotoxicity, but rather exhibited suppressor activity on the in vitro generation of cytotoxicity. In this stage, effect of LMS was not detected. For the induction of cytotoxic T-cells in vitro, the cooperation of nylon wool-nonadherent cells and antigen-presenting cells appeared to be necessary. Nylon wool-adherent cells exhibited the suppressor activity. LMS stimulated the activity of nonadherent cells and partially modulated the suppressor activity of adherent cells. These effects of LMS were suggested to result in the augmentation of the cytotoxicity of the spleen cells and the growth inhibition of the secondary tumors in Meth 1-bearing mice.

¹ To whom requests for reprints should be addressed.

Received 12/20/82. Accepted 8/ 5/83.