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Heterogeneity of Circulating Carcinoembryonic Antigen Analyzed by Sandwich-Enzyme Immunoassays with Different Specificities

Central Research Division, Takeda Chemical Industries, Ltd., Jusohonmachi, Yodogawa-ku, Osaka 532 [N. S., K. K.]; Shinko Hospital, Wakihama, Chuo-ku, Kobe 651 [S. T.]; and First Department of Biochemistry, School of Medicine, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka 814-01 [M. K., Y. M.], Japan

Nine monoclonal antibodies against carcinoembryonic antigen (CEA) were prepared and used to investigate the immunological and physicochemical heterogeneity of circulating CEA. Two of these, M221-73 and M272-11, recognized "CEA-distinctive" epitopes and they gave sandwich-enzyme immunoassays far less reactive with nonspecific cross-reacting antigen (NCA) and nonspecific cross-reacting antigen-2 (NCA-2). Sandwich-enzyme immunoassays selective for NCA-2 and NCA were also established using suitable monoclonal antibodies as competitive inhibitors against enzyme-labeled antibodies. The studies on the serum CEA levels determined by the "CEA-specific" assay indicated that CEA molecules recognized by M221-73 and M272-11 were generally found in the sera of both cancer patients and normal adults. CEA and related substances in sera were further analyzed by the sandwich-enzyme immunoassays after adsorption on M272-11-coupled immunosorbents and by gel filtration on an Ultrogel AcA-34 column. These studies revealed the presence of a CEA variant detected by the "NCA-2-selective" assay. The variant seemed to be closely related to NCA-2 because it lacked CEA-distinctive epitopes and had an apparent molecular weight similar to that of NCA-2. This variant appeared in the sera of some cancer patients and normal adults.

¹ To whom requests for reprints should be addressed, at Takeda Chemical Industries, Ltd., Central Research Division 17–85, Jusohonmachi 2-chome, Yodogawa-ku, Osaka 532, Japan.

Received 12/ 5/86. Revised 5/26/87. Accepted 6/23/87.