γ-Interferon Enhancement of Carcinoembryonic Antigen Expression in Human Colon Carcinoma Xenografts

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Abstract
Summary: Athymic nu/nu mice bearing a subcutaneous human colon cancer xenograft (WiDr, low CEA expression) were treated with γ-interferon (γIFN) at varying doses, frequencies, and periods of duration. CEA content (µg/g) and uptake of radiolabeled anti-CEA monoclonal antibody (MAB) (percent injected dose per gram, % ID/g) were measured at 48 h following administration of the MAB. The optimal enhancement of tumor CEA content and tumor localization of [111In] anti-CEA monoclonal antibody (MAB) was seen at γIFN doses of 100,000 U i.p. every 8 h for 4 days (4.7 µg/g; 29% ID/g) compared to control animals (0.9 µg/g; 10% ID/g). The effects of γIFN on CEA content and MAB localization were less pronounced when administered (a) at lower doses: 5,000 to 50,000 U i.p. every 8 h, (b) at varying frequencies: 300,000 U/day delivered in divided doses every 4 or 24 h, or (c) for varying periods: 2 or 6 days of therapy. In each case, the biologic effects on tumor CEA content and uptake of [111In]MAB correlated closely with the serum γIFN level. Therefore, we conclude that enhancement of in vivo CEA expression by γIFN may have clinical relevance for tumor imaging and therapy using radio labeled monoclonal antibodies.

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