IMMUNOSCINTIGRAPHY OF COLON CANCERS WITH THE HUMAN MONOCLONAL-ANTIBODY COU-1

The human monoclonal immunoglobulin M (IgM) antibody, COU-1 is obtaine d from a human-human hybridoma, which is derived by fusion between a h uman B-lymphoblastoid cell line and lymphocytes obtained from mesenter ic lymph nodes from a patient with colorectal cancer. COU-1 recognizes a 43 kilodaltons intracellulary located cytokeratin-like protein, str ongly expressed by adenocarcinoma tissue as compared to normal tissues . In tumor-bearing nude mice, antibody COU-1 labeled with I-125 has be en shown to accumulate in human colon cancer grafts when compared to h uman melanoma grafts and the normal mouse tissues. The observed accumu lation was sufficient to be detected externally by immunoscintigraphy. Antigen-binding fragments of the antibody were also prepared and were shown to accumulate in colon cancer grafts. Improved tumor to normal tissue ratio was seen with the half-monomeric fragment, and the time r equired was reduced. In the clinic, five patients with suspected color ectal cancer were given 2 mg of I-131-labeled COU-1. No adverse effect s were detected in any of the patients. Planar images were obtained on days 1, 2, 3, 5, and 7 after administration. The best images were obt ained on days 5 and 7. Tumors were localized by immunoscintigraphy in four of the patients. Of these patients, surgery revealed that three o f them had primary colorectal cancers located in the cecum, the ascend ing colon, and the rectum, respectively, while one patient had a pancr eatic cancer. The smallest lesion observed had a diameter of 3 cm. In one of the patients, otherwise undiagnosed multiple liver metastases w ere revealed by the immunoscintigraphy and confirmed at surgery. An x- ray of the colon performed on the fifth patient had shown a stricture in the descending colon suspected to be caused by cancer. The tumor sc intigraphy showed no accumulation of the antibody. Surgery revealed th at the stricture was caused by adherence and not cancer. These finding s are encouraging for further studies of this human monoclonal antibod y in cancer patients.