ENHANCED TAG-72 EXPRESSION AND TURNER UPTAKE OF RADIOLABELED MONOCLONAL-ANTIBODY CC49 IN METASTATIC BREAST-CANCER PATIENTS FOLLOWING ALPHA-INTERFERON TREATMENT

The IFNs, alpha and gamma, have been shown to enhance the tumor-associ ated glycoprotein (TAG-72) on adenocarcinoma cells is vitro and in mic e with human breast cancer xenografts, resulting in improved targeting of monoclonal antibody CC49, To determine the effect of IFN-alpha on biodistribution and tumor uptake of I-131-labeled CC49, patients with metastatic breast cancer were randomized to either receive or not rece ive IFN-alpha (3 million units daily for 14 days) by s.c. injection, T hree days after beginning IFN-alpha, all patients received 10-20 mCi o f I-131-CC49 (specific activity, 16.7 mCi/mg) i.v. Total-body Anger ca mera scans, along with total-body blood and plasma pharmacokinetics, w ere performed, Tumor biopsies were taken in all patients before and 48 h after IFN-alpha treatment, There were no significant differences in number of metastases imaged or whole-body, blood and plasma pharmacok inetics between IFN-alpha-treated and untreated patients, Quantitative immunohistochemistry on biopsy specimens from IFN-alpha-treated patie nts demonstrated a significant increase in mean +/- SEM TAG-72 express ion (45.7 +/- 19.4%) compared to patients that were not given IFN-alph a (1.3 +/- 0.95%; P < 0.05), Although slight increases in the percent injected dose of I-131-CC49 in tumor occurred after IFN-alpha-treatmen t, the changes were not significant at the P < 0.05 level. These data suggest that IFN-alpha may be useful in enhancing TAG-72 antigen expre ssion in vivo in humans, despite modest improvement in tumor uptake of CC49, possibly because of limited tumor access or other unknown facto rs.