A MOUSE HUMAN-CHIMERIC BISPECIFIC ANTIBODY-REACTIVE WITH HUMAN CARCINOEMBRYONIC ANTIGEN-EXPRESSING CELLS AND HUMAN T-LYMPHOCYTES/

A mouse/human-chimeric bispecific antibody, designated CBA-CEACD3, wit h dual specificities for carcinoembryonic antigen (CEA) and CD3, was g enerated by chemical cross-linking of a chimeric antibody specific for CEA to another chimeric antibody against CD3. Flow cytometric analysi s showed that CBA-CEACD3 can bind specifically to cells expressing CEA and to normal human peripheral blood mononuclear cells (HPBMCs) beari ng CD3, respectively. Furthermore, a cell to cell adhesion analysis by a colorimetric assay using the dye 4,5-dimethylthiazol-2-yl)-2,5-diph enyl-tetrazolium bromide (MTT) demonstrated that CBA-CEACD3 is able to bind CEA-producing cells to CDS-expressing cells, suggesting that bot h arms of CBA-CEACD3 are simultaneously working and can retarget T-cel ls to the tumor. In an additional colorimetric assay using MTT, this a ntibody was shown to effectively mediate CEA-expressing tumor cell kil ling by freshly isolated HPBMCs. Together these results demonstrate th at this chimeric bispecific antibody may serve as a potentially useful immunotherapeutic reagent for human CEA-producing cancers.