A monoclonal antibody-enzyme immunoassay for serum carcinoembryonic antigen with increased specificity for carcinomas.

A two-site monoclonal antibody-enzyme immunoassay (MEIA) for carcinoembryonic antigen (CEA) was developed that uses two monoclonal anti-CEA antibodies, which recognize two different epitopes in the peptide moiety of CEA. The assay was sensitive to 0.5 micrograms/liter and had a measuring range of 0.5-200 micrograms of CEA per liter. It was highly specific inasmuch as none of three known CEA-related substances, "nonspecific crossreacting antigens 1 and 2" (NCA-1 and NCA-2) and biliary glycoprotein I (BGP I), reacted in the assay. NCA-2 (meconium antigen) is very similar to CEA. None of five commercially available CEA assays were able to differentiate between CEA and NCA-2. With one exception (colon), normal tissue extracts did not react in the MEIA even when tested at very high concentrations. Sera from a total of 180 healthy individuals and patients with malignant and nonmalignant disease were analyzed for CEA levels by using the MEIA and in parallel a conventional radioimmunoassay. A significant increase in specificity for carcinomas was obtained with the MEIA. This was essentially due to a decrease of MEIA CEA values in sera from patients with nonmalignant disease. The CEA values in the group of carcinoma patients (colon, pancreas, lung, and breast) were the same in the two assays.