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Local and Systemic Effects during Interleukin-2 Therapy of Mouse Mammary Tumors¹

Department of Experimental Pathology, Roswell Park Memorial Institute, Buffalo, New York 14263-0001

The therapeutic effects of 12 daily peritumor injections of from 100 to 300,000 units of recombinant human interleukin-2 were tested against the syngeneic, immunogenic mammary carcinoma MC2 implanted s.c. into C3H/He mice. Local therapeutic effect on injected tumors was observed down to 300 units of interleukin-2 per injection. Cures of injected tumors were obtained with 1,000 units and more per injection. Systemic therapeutic effect on contralateral, uninjected tumors in treated mice was discernible at 5,000 units and more per injection. Hepatic periportal cellular swelling with mononuclear infiltration, and renal tubular edema were observed at 7,000 units or more per injection. Hepatic and renal repairs were rapid and complete with 50,000 units and less per injection. Hepatic necrosis developed above 50,000 units per injection. Deaths resulted from 100,000 units and more per injection. It is concluded that interleukin-2 can be a safe and effective therapeutic agent at a wide range of doses well below those that may be expected to have serious negative side effects.

¹ Supported by USPHS Grant CA29660 from the National Cancer Institute, and by grants from the Cetus Corporation and Concern Foundation.

² To whom requests for reprints should be addressed, at Department of Experimental Pathology, Roswell Park Memorial Institute, 666 Elm Street, Buffalo, NY 14263-0001.

Received 11/14/86. Revised 3/ 4/87. Revised 5/21/87. Accepted 5/27/87.