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Evaluation of the Antitumor Activity of Recombinant Human -Interferon Employing Human Melanoma Xenografts in Athymic Nude Mice

Schering-Plough Corporation, Bloomfield, New Jersey 07003 [P. P. T.]; and Southern Research Institute, Birmingham, Alabama 35255-5305 [S. D. H.]

Three human melanoma cell lines (G-361, HT-144, and SK-MEL-3) that were highly sensitive to growth inhibition in vitro by recombinant human interferon (rHulFN-) were adapted to grow as s.c. xenografts in athymic nude mice. Take rates were >90% for all three tumors, with in vivo doubling times of 15, 4, and 15 days for G-361, HT-144, and SK-MEL-3, respectively. Commencing 3 days posttumor implantation mice were treated with daily s.c. injection of rHulFN- for 30 days over a dose range of 2.4–326 megaunits/mouse/day at a site distinct from the tumor implant. Tumors were measured twice weekly and mice were observed daily for deaths and morbidity until day 60 postimplantation. No apparent antitumor activity was observed in either the G-361 or HT-144 tumors at any dose despite the achievement of high rHuIFN- blood levels. Intralesional treatment of the HT-144 xenograft with rHuIFN- at 240 megaunits/mouse/day did not signficantly retard tumor growth or increase lifespan. However, the SK-MEL-3 tumor showed a significant response at the 326-megaunit dose as noted by a tumor growth delay of 11.8 days in treated versus control animals and by an increased number of 60-day survivors. The tumor growth suppression appeared to be greater during the treatment period than during the subsequent observation period. Other experiments employing 326, 530, and 860 megaunits rHuIFN-/mouse/day in mice bearing the SK-MEL-3 tumor demonstrated tumor growth delays of 4.2, 4.8, and 19.8 days, respectively, suggesting a dose response. These data support the conclusions that (a) in vitro antiproliferative activity of rHuIFN- is not necessarily predictive of in vivo efficacy; and (b) relatively high doses of rHuIFN- appear to be required for demonstrating an in vivo antitumor effect in this model.

¹ To whom all correspondence should be addressed, at Schering-Plough Corporation, 60 Orange Street, Bloomfield, NJ 07003.

Received 1/30/87. Revised 6/ 1/87. Accepted 7/17/87.