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Interferon Enhancement of Radioimmunotherapy for Colon Carcinoma¹

Department of General Oncologic Surgery [J. A. K., B. G. B., R. R. B., J. D. B.], the Division of Radiation Oncology [J. Y. C. W.], the Department of Pathology [J. M. E.], the Division of Biostatistics [F. W.], and the Division of Radiology [L. E. W.], City of Hope National Medical Center, Duarte, California 91010, and Hybritech, Inc., San Diego, California 92126 [P. M. W.]

Recombinant human -interferon (IFN-) has recently been shown to enhance localization of radiolabeled monoclonal antibodies (MAb) to human colon carcinoma xenografts in athymic mice. The present study investigates the ability of -interferon to enhance radioimmunotherapy of a low carcinoembryonic antigen-expressing human colon cancer (WiDr) in athymic mice. Growth curve analysis, antibody localization, and dose estimation studies were performed. A significant tumor growth delay, measured as the time to reach 1.0 g, was noted for animals receiving specific anti-carcinoembryonic antigen ⁹⁰Y-MAb (ZCE025, 120 µCi) plus IFN- (61.8 days) as compared to animals that received specific ⁹⁰Y-MAb with phosphate-buffered saline (34.9 days; P < 0.005). IFN- (100,000 units) was given i.p. every 8 h for 2 days before and 4 days after ⁹⁰Y-MAb therapy. The time required to reach 1.0 g for animals treated with nonspecific ⁹⁰Y-MAb (ZME018) was significantly less either with (38.3 days) or without (34.4 days) IFN-. The difference was more apparent when compared to animals receiving IFN- alone (30.0 days) or phosphate-buffered saline alone (28.9 days; P < 0.001). Increased antibody localization in the tumors of animals treated with IFN- plus specific ⁹⁰Y-MAb (43.2% injected dose/g) was seen in comparison to animals treated with specific ⁹⁰Y-MAb without IFN- (18.2% injected dose/g). The estimate of radiation dose delivered to the tumors, based on biodistribution data over time, revealed significantly higher levels in animals treated with specific ⁹⁰Y-MAb with IFN- (2477 cGy) compared to animals treated without IFN- (1217 cGy). These results provide support for the use of -interferon as an immunomodulating agent prior to radioimmunotherapy.

¹ Supported in part by USPHS Training Grant CA09477, Program Project Grant CA43904, Cancer Center Core Grant CA33572, and by a grant from The Margaret Early Foundation, Los Angeles, CA.

² To whom requests for reprints should be addressed, at City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010.

Received 9/ 4/90. Accepted 2/22/91.

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