AN EPITOPE AN CARCINOEMBRYONIC ANTIGEN DEFINED BY THE CLINICALLY RELEVANT ANTIBODY PR1A3

The monoclonal antibody PR1A3 has been used successfully for in vivo i maging of colorectal cancers, and several properties associated with t his antibody, including minimal reactions of the antibody with circula ting antigen in patients' sera, differentiate it from anti-carcinoembr yonic antigen (CEA) antibodies used in similar studies. However, the a ntigen bound by PR1A3 was identified as CEA by analysis of somatic cel l hybrids and by antigen expression from yeast artificial chromosomes, cosmids, and cDNA clones. The molecular weight, presence of a glycosy l-phosphatidylinositol anchor, elevation of surface expression by gamm a-interferon, and N-terminal amino acid sequence all confirmed the ant igen identification as CEA. A series of biliary glycoprotein-CEA hybri d proteins was produced which demonstrated that the epitope bound by t he antibody was at the site of membrane attachment and involved parts of the glycosyl-phosphatidy-inositol anchor and the B3 domain of CEA t o form a conformational epitope. Access to this epitope, although poss ible when the antigen was on the cell surface, appeared to be blocked when CEA was released from the cell. The nature and location of the ep itope on CEA are proposed to be responsible for the unique properties of the antibody.