Characterization of second-generation monoclonal antibodies against carcinoembryonic antigen

Abstract

Background. A second‐generation panel of anti–carcinoembryonic antigen (CEA) monoclonal antibodies (MoAb) has been generated, and the specificity has been compared with that of the first panel of MoAb used to differentiate meconium antigen (MA) from CEA. Methods and Results. Four of the MoAb had similar specificities to the first‐generation panel of NP MoAb. MN‐15, like its first‐generation equivalent, NP‐1, reacts with normal cross‐reactive antigen (NCA), MA, and CEA; both MN‐15 and NP‐1 react strongly with granulocytes. MN‐2 has properties similar to Class II NP‐2, being reactive with MA and CEA, cross‐blocking binding to CEA by NP‐1, and having low reactivity with granulocytes; both NP‐2 and MN‐2 stain granulocytes in frozen tissue sections but show minimal staining of granulocytes in sections fixed in formaldehyde solution and embedded in Paraplast (Fischer Scientific, Pittsburgh, PA). MN‐14 demonstrates properties similar to the Class III anti‐CEA–specific MoAb, NP‐4, being unreactive with NCA and MA. MN‐14, as compared with NP‐4, demonstrated significantly superior tumor targeting in a human colon tumor xenograft model and consistently stronger staining of frozen sections of colon cancer. A fifth MoAb, MN‐3, had properties uniquely different from the NP series of MoAb, reacting strongly with granulocytes but not demonstrating the liquid‐phase ion‐sensitivity binding of CEA exhibited by MN‐15 and NP‐1. Conclusions. MN‐14 is being evaluated for radioimmunodetection of and radioimmunotherapy for CEA‐containing cancers, whereas MN‐3 is being studied for the radioimmunodetection of occult infections and sites of inflammation.