[In vivo application of monoclonal antibodies in the management of human carcinomas].
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.
Ohuchi
N
N
2nd Dept. of Surgery, Tohoku University School of Medicine.
Colcher
D
D
Schlom
J
J
D000911:Antibodies, Monoclonal; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary; D006801:Humans; D007553:Isotope Labeling; D011877:Radionuclide Imaging
D000911:Antibodies, Monoclonal