Epitopes of carcinoembryonic antigen (CEA) defined by monoclonal antibodies.

Of 15 anti-CEA monoclonal antibodies, the first 8 were reactive only with CEA, while the remaining 7 antibodies reacted with epitopes commonly expressed on CEA and the normal cross-reacting antigen, NCA. Separate and distinct, conformation-dependent (i.e. susceptible to reduction and alkylation), CEA-associated epitopes were identified using antibodies 1, 2 and 3. Antibodies 4 to 7 defined a series of conformation-independent epitopes which were topographically closely related on the CEA molecule. Antibody number 8 reacted with a separate determinant found on CEA but not NCA, and this also was resistant to reduction and alkylation. Antibody number 9 defined an epitope which was commonly expressed on CEA and NCA. This epitope was conformation-dependent and was the most sensitive to NaIO4. The remaining antibodies, 10 to 15, which also reacted with CEA and NCA, defined an immunodominant region of these molecules since the 6 epitopes were clearly closely related, but not necessarily identical. The findings presented establish a rational basis for the selection of combinations of anti-CEA antibodies for diagnostic and therapeutic purposes.