In this study, the
breast carcinoma-reactive
monoclonal antibody 15A8 and a site-specific
immunoconjugate of the antibody, 15A8-glycyl-tyrosyl-(N-epsilon-diethylenetriamine pentaacetic acid)-lysine (15A8-GYK-DTPA), were characterized by immunohistological methods for reactivity with normal and neoplastic human tissues and normal cynomolgus monkey tissues. In addition, 15A8-GYK-DTPA labeled with 111In was assessed by in vivo imaging and pharmacokinetic studies for localization to human
tumor xenografts in nude mice. The native antibody and the site-specific
immunoconjugate exhibited similar limited reactivity with normal human tissues. Specifically, epithelial structures, including normal breast epithelium, lung alveoli, bronchial epithelium and glands, liver bile ducts, pancreatic ducts, kidney distal and collecting tubules, epidermal and esophageal epithelium, endometrial glands, and thymic Hassall's corpuscles, were reactive. Normal monkey tissues stained with 15A8 exhibited a similar pattern of reactivities. Antibody 15A8 reacted broadly with epithelium-derived
tumors; more than 60% of the cells in all of the breast, colon, non-small cell lung, ovarian, prostate, bladder, and
renal carcinomas tested expressed the
antigen. In contrast, a variety of nonepithelial
neoplasms, including
lymphomas,
melanomas,
sarcomas, and small cell lung
carcinomas, were nonreactive. 15A8-GYK-DTPA-111In administered i.v. rapidly localized to and imaged both MX-1 and MCF-7 human
breast carcinoma xenografts in nude mice, reaching maximal levels of about 20% of injected dose/g of
tumor within 4 days. No unusual localization to any nontumor tissue or organ was seen; the level of radioactivity in the normal tissues and organs was at or below that seen in the blood. Furthermore, the
immunoconjugate did not accumulate in xenografts of the
antigen-negative
breast carcinoma ZR-75-1, which indicates that
tumor localization was
antigen specific. Pharmacokinetic studies in cynomolgus monkeys suggested that significant amounts of 15A8-GYK-DTPA-111In did not localize to normal epithelia and demonstrated that the
immunoconjugate was not toxic. These findings suggest that antibody 15A8 may be useful in the diagnosis and
therapy of
breast cancer and possibly other
carcinomas.