Epitope specificity and cross-reactivity pattern of a large series of monoclonal antibodies to carcinoembryonic antigen

Monoclonal antibodies (MAbs) were produced against purified carcinoembryonic antigen (CEA) from liver metastases of colo-rectal and lung adenocarcinoma. Three and eight anti-CEA MAbs from the two groups were analyzed in detail All antibodies were IgGl. With one exception they recognized epitopes present on all eight individual CEA preparations investigated irrespective of whether they were from colo-rectal or lung carcinoma. The exceptional MAb reacted with an epitope present on most but not all CEA preparations. With two, or possibly three, exceptions the MAbs recognized conformation dependent epitopes in the peptide moiety of CEA. One MAb reacted strongly with reduced and carboxymethylated CEA but only weakly with native CEA. Four MAbs appeared to be CEA-specific in that they did not react with any of the known CEA-cross-reactive substances including nonspecific cross-reactive antigen of 160,000 mol. wt (NCA-160). A total of nine different epitopes were detected in native CEA using this and our previous series [Hedin A., Hammarström S. and Larsson Å. (1982) Molec. Immun. 19, 1641] of anti-CEA MAbs. With one exception practically all molecules (70–90%) in purified CEA preparations contained these epitopes.