Murine
monoclonal antibody (MAb)
B72.3 was prepared using a membrane-enriched fraction of
breast carcinoma as the immunogen. MAb
B72.3 has been previously shown, by in vitro assay, to have a high degree of specificity for
carcinomas of the colon, ovary, breast and stomach versus normal adult tissues. The reactive
antigen (termed TAG-72) has been purified and characterized.
B72.3 IgG was radiolabeled with 131I and utilized for the in situ detection of
colorectal cancer metastases. The radiolocalization of MAb
B72.3 administered intravenously (i.v.) into
colorectal cancer patients was sufficient to allow detection of more than 50% of the lesions by gamma-scanning. Radiolocalization indices (RI) (i.e., cpm 131I-labeled MAb/g of
tumor versus cpm/g of normal tissue) were obtained by direct analyses of biopsy materials. Using an RI of greater than 3 to indicate positive localization,
tumor lesions at various sites from 17/20 patients were positive. Seventy percent (99/142) of the
tumor lesions had RIs of greater than 3, while only 12 of 210 normal tissues had RIs of greater than 3. 131I-B72.3
IgG was also intraperitoneally (i.p.) administered to 10 patients with
colorectal cancer. Specific
tumor localization via gamma-scanning (confirmed at surgery) was observed in 7/10 patients. Three of the 7 patients were negative for
tumor detection by both CAT scan and X-ray but were positive for
tumor localization via gamma-scanning of i.p.-administered MAb
B72.3. Direct analyses of biopsy specimens of
carcinoma and normal tissues demonstrated ratios greater than 70:1 for
tumor MAb localization versus normal tissues. No clinical toxicity or adverse reactions were observed with the MAb when administered i.v. and i.p. These results thus demonstrate the efficacy of i.v. and i.p.-administered MAb
B72.3 for the radiolocalization as well as potential use of MAb
B72.3 in protocols aimed at
tumor targeting and in MAb-guided
therapy for human epithelial
malignancies.