285. Concanavalin A That Bears Direct Cytotoxicity and Immunomodulating Activity Via Mannose-Specific Cellular Binding Has Therapeutic Effect in a Murine In Situ Hepatoma Model
Authors: Chih-Peng Chang, Ying-Tai Jin, Huan-Yao Lei
Journal: Molecular Therapy (2006)

Hepatocellular carcinoma (HCC) is one of the human cancers with poor prognosis and is a leading cause of death in certain areas of Africa and Asia. Unfortunately, there is no satisfactory therapy for HCC patients. Concanavalin A (Con A), a lectin with mannose and glucose binding specificity, was tested for therapeutic effects in a murine in situ hepatoma model. Con A was able to bind to several types of tumor cells, including HCC, and as a result to induce cell death. Intravenous injection with a non-lethal dose (7.5 mg/kg, twice at 3-day intervals beginning at day 7) of Con A could inhibit liver tumor nodule formation, prolong the mice survival and cure 20-30% of the mice. Con A also had partial therapeutic effects on large tumor burden mice. The liver tumor growth inhibition by Con A treatment in immunocompetent mice is CD8+ cell-dependent and the cured mice were able to resist challenge by the same tumor, suggesting a induction of tumor cell-specific memory. Moreover the liver tumor growth inhibition was also observed in severe combined immune deficiency mice in a dose-dependent manner. Other lectins with mannose or glucose specific-binding ability, like PSA and LCA, were also showed to inhibit the liver tumor growth in vivo. The differential staining by FITC-Con A, -PSA and –LCA in human hepatoma tissue might indicate the potential role of lectins on HCC therapy. We concluded that a lectin like Con A that bears both direct cytotoxicity and immunomodulating activity can be used a new anti-hepatoma agent therapeutically. Hepatocellular carcinoma (HCC) is one of the human cancers with poor prognosis and is a leading cause of death in certain areas of Africa and Asia. Unfortunately, there is no satisfactory therapy for HCC patients. Concanavalin A (Con A), a lectin with mannose and glucose binding specificity, was tested for therapeutic effects in a murine in situ hepatoma model. Con A was able to bind to several types of tumor cells, including HCC, and as a result to induce cell death. Intravenous injection with a non-lethal dose (7.5 mg/kg, twice at 3-day intervals beginning at day 7) of Con A could inhibit liver tumor nodule formation, prolong the mice survival and cure 20-30% of the mice. Con A also had partial therapeutic effects on large tumor burden mice. The liver tumor growth inhibition by Con A treatment in immunocompetent mice is CD8+ cell-dependent and the cured mice were able to resist challenge by the same tumor, suggesting a induction of tumor cell-specific memory. Moreover the liver tumor growth inhibition was also observed in severe combined immune deficiency mice in a dose-dependent manner. Other lectins with mannose or glucose specific-binding ability, like PSA and LCA, were also showed to inhibit the liver tumor growth in vivo. The differential staining by FITC-Con A, -PSA and –LCA in human hepatoma tissue might indicate the potential role of lectins on HCC therapy. We concluded that a lectin like Con A that bears both direct cytotoxicity and immunomodulating activity can be used a new anti-hepatoma agent therapeutically.