Activated macrophages are responsible for the tumor-inhibitory effect in mice receiving intravenous injection of OK-432

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Abstract
Mouse spleen cells, either pretreated in vitro with 100 U/ml of OK-432-induced IFN [interferon] gamma for 18 h or obtained from mice 24 or 48 h after i.v. injection of OK-432 (100 .mu.g/mouse), were examined for their anti-tumor effect by Winn''s neutralization assay against Meth-A tumor cells in BALB/c mice. Spleen cells treated in vitro or obtained in vivo 24 h after i.v. injection clearly neutralized the growth of admixed Meth-A cells. Two booster injections of 200 U IFN gamma near the tumor site accelerated this neutralizing effect. In order to determine the effector subpopulation, inhibitory spleen cells were treated with either anti-Thy-1 monoclonal antibody plus complement, antiasialo GM1 serum plus complement or with adherence on plastic plates followed by Sephadex G-10 column treatment. The effector cell activity in Winn assay was lost only after the removal of macrophages through plastic plate adherence and Sephadex G-10 column treatment, but not after anti-Thy-1 or anti-asialo GM1 treatment, with either in vitro- or in vivo-treated spleen-cell populations. The growth of Meth-A cells was inhibited not only by these activated macrophages in Winn''s assay, but also by adoptive transfer of OK-432-induced cytotoxic macrophages intralesionally 4 days after the implantation of 1 .times. 106 Meth-A cells. The systemic action of OK-432 can be explained by the effect of induced IFNgamma, through the activation of macrophages.