The
monoclonal antibody PR1A3 has been used successfully for in vivo imaging of
colorectal cancers, and several properties associated with this antibody, including minimal reactions of the antibody with circulating
antigen in patients' sera, differentiate it from anti-
carcinoembryonic antigen (CEA)
antibodies used in similar studies. However, the
antigen bound by PR1A3 was identified as CEA by analysis of somatic cell hybrids and by
antigen expression from yeast artificial chromosomes, cosmids, and
cDNA clones. The molecular weight, presence of a
glycosyl-phosphatidylinositol anchor, elevation of surface expression by
gamma-interferon, and N-terminal amino acid sequence all confirmed the
antigen identification as CEA. A series of biliary
glycoprotein-CEA hybrid
proteins was produced which demonstrated that the
epitope bound by the antibody was at the site of membrane attachment and involved parts of the
glycosyl-phosphatidylinositol anchor and the B3 domain of CEA to form a conformational
epitope. Access to this
epitope, although possible 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
epitope on CEA are proposed to be responsible for the unique properties of the antibody.