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Effect of Hyperthermia on Combination Interferon Treatment: Enhancement of the Antiproliferative Activity against Murine B-16 Melanoma^{1, 2,}

Department of Microbiology, The University of Texas Medical Branch, Galveston, Texas 77550 [W. R. F., C. M. F.], and Laboratory of Experimental Pathology, National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland 21701 [T. D. G.]

Previous studies have evaluated the effects of hyperthermia on the antiproliferative activity of interferon. The activities of all three types of interferon have been shown to be synergistically enhanced by hyperthermic conditions. Further, the antiproliferative activity of interferon has been shown to be synergistically enhanced by combinations of - plus - or ß-interferon. The question remained whether combining these two methods of enhancing interferon activity would lead to an even higher level of enhancement of antiproliferative activity or to an antagonism of their separate effects. To address this question, mouse B-16 melanoma cells were cloned at 37.3°C and at 39.4°C in the presence of various combinations of murine /ß- and -interferon. Potentiation of interferon's antiproliferative activity by combination interferon treatment was found to occur at both temperatures. Moreover, the level of potentiation was synergistically enhanced by hyperthermic conditions. The results suggest that a combined treatment regimen of hyperthermia and combination interferon therapy (- plus - or ß-interferon) may provide a highly potent antitumor effect.

¹ Supported by USPHS Grant CA26475 awarded by the National Cancer Institute, Department of Health and Human Services.

² The abbreviations used are: IFN-, -ß, -/ß, and -, -, ß-, /ß-, and -interferons; MuIFN-/ß and -, murine /ß- and -interferons; HuIFN-, human -interferon.

Received 8/26/85. Revised 11/26/85. Accepted 12/11/85.