Enhanced TAG-72 expression and tumor uptake of radiolabeled monodonal antibody CC49 in metastatic breast cancer patients following α-interferon treatment

The IFNs, α and γ, have been shown to enhance the tumor-associated giycoprotein (TAG-72) on adenocarcinoma cells in vitro and in mice with human breast cancer xenografts, resulting in improved targeting of monoclonal antibody CC49. To determine the effect of IFN-α on biodistribution and tumor uptake of ¹³¹I-labeied CC49, patients with metastatic breast cancer were randomized to either receive or not receive IFN-α (3 million units daily for 14 days) by s.c. injection. Three days after beginning IFN-α, all patients received 10-20 mCi of ¹³¹I-CC49 (specific activity, 16.7 mCi/mg) i.v. Total-body Anger camera scans, along with total-body blood and plasma pharmacokinetics, were performed. Tumor biopsies were taken in all patients before and 48 h after IFN-α treatment. There were no significant differences in number of metastases imaged or whole-body, blood and plasma pharmacokinetics between IFN-ä-treated and untreated patients. Quantitative immunohistochemistry on biopsy specimens from IFN-α-treated patients demonstrated a significant Increase in mean ± SEM TAG-72 expression (45.7 ± 19.4%) compared to patients that were not given IFN-α (1.3 ± 0.95%; P < 0.05). Although slight increases in the percent injected dose of ¹³¹I-CC49 in tumor occurred after IFN-α-treatment, the changes were not significant at the P < 0.05 level. These data suggest that IFN-α may be useful in enhancing TAG-72 antigen expression in vivo in humans, despite modest improvement in tumor uptake of CC49, possibly because of limited tumor access or other unknown factors.