Antitumor effect of monoclonal antibody-carboplatin conjugates in nude mice bearing human ovarian cancer cells

Abstract

Background. The antitumor effect and toxicity of immunoconjugates were studied in nude mice bearing a human ovarian cancer cell line, OVA-1. Methods. We studied the tissue distribution of an anticytokeratin-8 monoclonal antibody (6D7) in OVA-1-bearing nude mice by giving 6D7 labelled with 125 I. The immuno conjugate consisted of 6D7 and carboplatin (6D7-conjugate), coupled via carboxymethyl dextran, and this was intraperitoneally administered to OVA-1 bearing nude mice. The tumor volume and the body weight were measured for 5 weeks. Tissue platinum concentrations in the OVA-1 tumor, blood, liver, kidney, and spleen, were measured from 3 to 120 min after administration of the conjugate. The results were compared with those in nude mice treated with nonspecific mouse IgG coupled with carboplatin (IgG-conjugate) or carboplatin alone. Results. The coupling rate of the drug to 6D7 was approximately 80%, and was stable over several measurements at various times. In-vivo accumulation of 6D7 labelled with 125 I in the OVA-1 tumors was significantly higher than that in mice that received nonspecific mouse-IgG-125 I, with tumor/ blood radioactivity ratios of 14.0 and 1.28, respectively. The tumor growth rate in mice that were administered 6D7-conjugate was (at a maximum) 40% lower than the tumor growth rate in mice administered carboplatin. The body weight of the mice that received 6D7-conjugate did not decrease during the 5-week observation period, while the body weight of the mice that received carboplatin decreased by a maximum of 10%. In addition, upon administration of 6D7-conjugate, the platinum concentration in the tumor was maintained for a longer period than after the administration of carboplatin alone. Conclusions. The tumor growth suppression effect was significantly higher in the mice bearing the OVA-1 tumor that received 6D7-conjugate than in the animals that received carboplatin alone. This difference could be caused by differences in the platinum concentrations in the tumor between the two groups.