Recombinant CD40 ligand therapy has significant antitumor effects on CD40-positive ovarian tumor xenografts grown in SCID mice and demonstrates an augmented effect with cisplatin

CD40 is a member of the tumor necrosis factor receptor family and was first identified with a monoclonal antibody raised against bladder carcinoma. Re combinant human CD40L has been shown previously to have a direct antitumor effect on an ovarian cancer cell line and ovarian carcinoma cells isolated from ascites fluid. We show here that rhuCD40L inhibits the growth of sever al ovarian adenocarcinomas derived from surgical specimens and grown as xen ografts in severe combined immunodeficient mice. Two 14-day treatment cycle s were more effective than one. This effect is apparently not mediated by n atural killer cells, because blocking natural killer cell activity by antia sialo GM-I did not diminish this effect. In addition to suppression of tumo r growth, treatment with rhuCD40L resulted in an increased expression of Fa sL, an increase in apoptosis, and histological changes including increased fibrosis and areas of tumor destruction. Using this model, we examined the efficacy of rhuCD40L in combination with chemotherapeutic agents. The antit umor effect of rhuCD40L in combination with 4 mg/kg cisplatin (CDDP) was in creased over the effect of CDDP alone. Furthermore, rhuCD40L increased the efficacy of a suboptimal dose of CDDP (2mg/kg) such that it matched that of high-dose CDDP alone. These data suggest a role for rhuCD40L therapy in co mbination with platinum based regimens for primary treatment of epithelial ovarian tumors.