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In Vivo Antitumor Activity of Multiple Injections of Recombinant Interleukin 2, Alone and in Combination with Three Different Types of Recombinant Interferon, on Various Syngeneic Murine Tumors¹

Chemotherapy Division, National Cancer Center Research Institute [M. I., A. H.], and Department of Internal Medicine, National Cancer Center Hospital [M. S., T. T., N. S.], Tsukiji 5-chome, Chuo-ku, Tokyo 104, Japan

We have used several transplantable experimental murine tumors to evaluate the potentiation of antitumor activity by a combination of human recombinant interleukin 2 (rHIL2) and recombinant interferons (rIFNs). The combination of rHIL2 and either human hybrid recombinant -interferon A/D (rIFN- A/D) or mouse recombinant ß-interferon (rIFN-ß) induced the s.c. adenocarcinoma 755, which had been established for 8 days, to regress, although rHIL2 or the rIFNs alone hardly inhibited the tumor's growth. Eight injections of the rHIL2-rIFN- A/D combination cured 38% of the tumor-bearing mice. The rHIL2-rIFN-ß combination achieved a complete cure only when given in more than 13 injections. The administration of rHIL2 and mouse recombinant -interferon (rIFN-) markedly inhibited tumor growth of the s.c. established adenocarcinoma 755, but did not cure any of the mice. Other tumors, B16-F10 melanoma, and colon tumors 38 and 26 responded almost as well to a rHIL2-rIFN- A/D or -ß combination, but not to a rHIL2-rIFN- combination. The growth of Lewis lung carcinoma was inhibited to a lesser extent by all combinations, for which there were no long-term survivors.

The combination therapy of rHIL2 and rIFN-ß produced a marked regression of the tumor in beige mice which have low natural killer activity, suggesting the activated natural killer cells not to be responsible for the therapeutic effect. And T-cell immunity may be important in the regression of s.c. established tumors, because of the lesser potentiation of antitumor activity in athymic mice.

These results demonstrate that combination therapies of rHIL2 and rIFN- A/D or -ß can function synergistically in the various s.c. established murine tumor systems and give further evidence in support of their clinical potential.

¹ This research was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare and from the Ministry of Education, Science, and Culture, Japan.

Received 5/20/87. Revised 8/27/87. Accepted 10/ 9/87.

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