Production of monoclonal antibodies to serum antigens in colorectal carcinoma

Abstract

Two monoclonal antibodies (mAb) to colorectal cancer were produced using a novel immunization technique. This involved immunizing mice with whole serum obtained from patients with cancer of the colon (three with metastatic disease) and resulted in antibodies which were reactive with colonic tumor tissue by immunoperoxidase testing. Two mAbs (O-1, I-1) were isolated which were non-reactive with normal tissue and with tissues obtained from subjects with benign disease but were reactive with 34/50 (formalin-fixed) colon carcinoma specimens. Further testing on cell lines and other malignant tumors suggested both mAbs detect carcinoembryonic antigen (CEA) as their reactivities were similar to a known anti-CEA antibody, and they reacted with CEA in a solid-phase radioimmunoassay. The two mAbs were found to react with the same or closely associated epitopes on CEA by competitive tests. As the anti-CEA antibodies were made to serum (rather than tissue) CEA, it was possible that unique, highly specific mAb has been produced, particularly as there was a selective reaction of the mAbs for malignant but not normal tissues. A serum test with mAb I-1 was developed which detected raised serum CEA levels in 3/24 patients with benign colonic lesions, 7/19 patients with pancreatic cancer, 5/25 patients with colonic cancer but not in 20 normal individuals. There was direct correlation between these results and a commercially available CEA test kit.