Immunoscintigraphy of colon cancers with the human monoclonal antibody cou-1

Abstract

The human monoclonal immunoglobulin M (IgM) antibody, COU-1 is obtained from a human-human hybridoma, which is derived by fusion between a human B-lymphoblastoid cell line and lymphocytes obtained from mesenteric lymph nodes from a patient with colorectal cancer. COU-1 recognizes a 43 kilodaltons intracellularly located cytokeratin-like protein, strongly expressed by adenocarcinoma tissue as compared to normal tissues. In tumor-bearing nude mice, antibody COU-1 labeled with 125I has been shown to accumulate in human colon cancer grafts when compared to human melanoma grafts and the normal mouse tissues. The observed accumulation 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 required was reduced. In the clinic, five patients with suspected colorectal cancer were given 2 mg of 131I-labeled COU-1. No adverse effects 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 obtained on days 5 and 7. Tumors were localized by immunoscintigraphy in four of the patients. Of these patients, surgery revealed that three of them had primary colorectal cancers located in the cecum, the ascending colon, and the rectum, respectively, while one patient had a pancreatic cancer. The smallest lesion observed had a diameter of 3 cm. In one of the patients, otherwise undiagnosed multiple liver metastases were 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 scintigraphy showed no accumulation of the antibody. Surgery revealed that the stricture was caused by adherence and not cancer. These findings are encouraging for further studies of this human monoclonal antibody in cancer patients.