Definition by Monoclonal Antibodies of a Repertoire of Epitopes on Carcinoembryonic Antigen Differentially Expressed in Human Colon Carcinomas versus Normal Adult Tissues

Abstract

Monoclonal antibodies (MAbs) designated COL-1 through 15 have been generated and characterized and show a strong degree of selective reactivity for human colon carcinomas versus normal adult tissues. To prepare the MAbs, mice were immunized with extracts or membrane-enriched fractions of biopsy material from either primary or metastatic colon carcinoma lesions. The fifteen COL MAbs, all of the immunoglobulin G subclasses 1, 2a, or 2b, reacted with purified carcinoembryonic antigen in solid-phase radioimmunoassay and by immunoblotting, but none reacted with human polymorphonuclear leukocytes or certain spleen preparations previously shown to be rich in carcinoembryonic antigen-related or cross-reactive antigens. MAbs COL-1 through 15 could be divided into at least five groups based on their differential range of reactivities to the surface of colon carcinoma cells or other carcinoma cell preparations. The COL MAbs were tested via immunoperoxidase with a wide range of primary and metastatic colon carcinomas, benign or dysplastic colon lesions, and 34 normal adult tissues. With few exceptions, the COL MAbs tested in this manner showed reactivity only to the primary and metastatic colon carcinomas. These studies thus provide a well-characterized repertoire of MAbs that are well suited for potential clinical trials involving the radiolocalization and possibly therapy of human colon carcinoma lesions. The fact that at least five epitopes are being recognized also provides the opportunity for testing the efficacy of cocktails of the COL MAbs toward these goals.