COMPLETE REGRESSION OF HUMAN FIBROSARCOMA XENOGRAFTS AFTER LOCAL NEWCASTLE-DISEASE VIRUS THERAPY

We have recently demonstrated that a single local injection of the avi an pathogen Newcastle disease virus (NDV; strain 73-T) causes complete regression of human neuroblastoma xenografts in athymic mice (R. M. L orence, K. W. Reichard, B. B. Katubig, H. M. Reyes, A. Phuangsab, B. I C Mitchell, C. J. Cascino, R. J. Waiter, and M. E. Peeples. J. Natl. C ancer Inst., 86: 1228-1233, 1994). In this report, we tried to determi ne if this ill vivo antineoplastic effect of NDV extends to human sarc omas. Athymic mice with s.c. HT1080 fibrosarcoma xenografts (7-14 mm) were randomly divided into two groups and treated i.t. with a single i njection of either 10(7) plaque-forming units of NDV or phosphate-buff ered saline. Complete tumor regression occurred in 8 of 10 mice treate d with NDV while unabated tumor growth occurred in all 9 mice treated with phosphate-buffered saline (P < 0.001). To determine if complete t umor regression was long lasting, the 8 mice were monitored for 1 year , during which time no tumor recurred. To test the antitumor effects o f NDV on tumors derived from a fresh human sarcoma, a similar experime nt was performed in athymic mice using TH15145 synovial sarcoma xenogr afts at their first and second passages. Of 9 mice with TH15145 xenogr afts, a single i.t. injection of NDV (10(7) plaque-forming units) caus ed complete regression of 3 tumors and > 80% regression in 3 more tumo rs. In contrast, tumors in all 5 mice treated with phosphate-buffered saline exhibited unabated growth (P < 0.03 for > 80% tumor regression) . Since HT1080 fibrosarcoma cells express the N-ras oncogene, we explo red the effects that transfection of this oncogene has on the sensitiv ity to NDV. Cultured human fibroblasts that were made tumorigenic foll owing N-ras-transfection were found to be 1000-fold more sensitive to NDV than normal fibroblasts in a cytotoxicity assay. Oncogene expressi on by the HT1080 fibrosarcoma may therefore contribute to the long-las ting complete regression of this sarcoma following a single local inje ction of NDV.