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Antitumor Activity of -Interferon in Ascitic and Solid Tumor Models of Human Ovarian Cancer

Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A3PX, United Kingdom [S. T. A. M., N. E., G. S., F. R. B.]; Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS, United Kingdom [R. G. K.]; and Centre de Recherche, Roussel UCLAF, 111 Route de Noisy, Romainville, 93230, France [D. L.]

We have investigated the action of recombinant human -interferon (rHuIFN-) against human ovarian cancer xenografts growing as ascites or as bulky solid i.p. tumors in nude mice. Both forms of the disease responded to i.p. rHuIFN- with significant increases in mouse survival time, and in 2 of 3 ascitic models the mice were cured of peritoneal disease. The activity of rHuIFN- was dose and schedule dependent, and xenografts derived from 3 different patients showed a heterogeneity of response. Peak i.p. levels of rHuIFN- in nude mice bearing multiple i.p. solid tumors were similar to those found in ovarian cancer patients receiving i.p. rHuIFN-, but clearance was more rapid in the mice. Rat -interferon had no antitumor activity at the same doses and schedules although it had some biological activity in the nude mice. Histological examination of treated tumors revealed increased necrosis and loss of cellular organization with large areas of hypocellular epithelial mucin. These changes were preceded by a fall in tumor tryptophan and a rise in tumor kynurenine. We conclude that rHuIFN- has a direct dose related antitumor effect on ovarian cancer xenografts that is preceded by increased metabolism of tryptophan.

Received 7/18/91. Accepted 10/ 1/91.

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