STUDIES ON ANTITUMOR ACTIVITY OF CORYNEBACTERIUM KUTSCHERI

The antitumor effect of Corynebacterium kutscheri was evaluated in mice by the administration of formalin-killed whole cell (FK-CK) or subcellular fraction named CK・m (mitogen derived from C. kutscheri). In these studies, two systems of mouse vs tumor cell (outbred ddY vs Ehrlich ascites carcinoma cell, inbred CDF₁ vs P388 leukemia cell) were used. Treatment of mice in the dose range of greater than 10⁶ bacterial cells or 20 μg of CK・m per mouse conferred substantial protection on both mice. The enhanced cytotoxicity of peritoneal exudate cells played a leading role in the initial phase of antitumor activity. The Winn assay disclosed that antitumor activity was attributable to nonadherent splenocytes whose activity was impaired by treatment with anti-T cell antibody and complement. The fact that the generation of effector cells paralleled that of the delayed-type hypersensitivity to this bacterium may suggest that the antitumor activity of C. kutscheri is mediated in part by T cell. The isolation and characterization of biological activities of the active component of C. kutscheri were attempted. The antitumor activity was confined to the subcellular particle fraction of this organism and associated with a molecule of glycoprotein nature (38,000 Dalton) isolated from this fraction by affinity chromatography with Concanavalin A-Sepharose 4B. This substance exerted mitogenic effect on C3H/HeJ splenocytes and T cells and further exhibited antitumor activity on P388 leukemia cell in CDF₁ mice. The Winn assay disclosed that the antitumor activity induced by this material was dependent on L3T4 T cells. Furthermore, both the mitogenic and antitumor activity of this moiety were resistant to heating at 100℃ for 30 min or RNase digestion, but sensitive to trypsin digestion, low or high pH. These results indicate that the antitumor activity of C. kutscheri is attributable to the heat-stable glycoprotein moiety which can directly stimulate T cells and macrophages