IN-VITRO AND IN-VIVO CHARACTERIZATION OF 2 MOUSE-HUMAN CHIMERIC ANTIBODIES WITH HIGH SPECIFICITY AND AFFINITY FOR CARCINOEMBRYONIC ANTIGEN

We evaluated in vitro immunoreactivities and in vivo tumor accumulatio n of two mouse-human chimeric antibodies to carcinoembryonic antigen ( CEA), designated Ch F11-35 and Ch F11-39, both of which have recently been generated by ourselves and shown to exhibit the same high specifi city and affinity for CEA as those of their parental mouse monoclonal antibodies (MAbs), respectively. In vitro cell binding assays of both I-l25-labeled chimeric antibodies against a human CEA-producing gastri c carcinoma cell line, MKN-45, demonstrated immunoreactivities almost identical with those of the parental MAbs. The two chimeric antibodies showed a potent antibody dependent cell-mediated cytotoxicity (ADCC) with human peripheral blood mononuclear cells as effecters against the MKN-45 cells. In vivo biodistribution of the two I-125-labeled chimer ic antibodies was separately studied in athymic nude mice bearing the MKN-45 xenografts. The percent of injected dose per gram of tumor tiss ue, tumor:blood ratios, and tumor:organ ratios obtained for both antib odies were extremely higher than those obtained for I-125-labeled huma n IgG, an isotype-matched control, indicating that the two chimeric an tibodies were specifically localized in tumor tissues xenografted in a thymic nude mice. These results demonstrate that the two chimeric anti bodies may serve as potential useful diagnostic and/or therapeutic rea gents.