© 1988 by Oxford University Press
Journal of the National Cancer Institute, Vol. 80, No. 16, 1305-1312,
October 19, 1988
© 1988 Oxford University Press
Newcastle Disease Virus as an Antineoplastic Agent: Induction of Tumor Necrosis Factor-
and Augmentation of Its Cytotoxicity2,3
2Supported by a fellowship to R. M. Lorence from the James Ewing Foundation (Society of Surgical Oncology); by Public Health Service grant AG-06246 from the National Institute on Aging, National Institutes of Health, Department of Health and Human Services; and by grant 86-CRCR-1-2003 from the Department of Agriculture.
4Laboratory of Immunophysiology, Department of Animal Sciences, University of Illinois Urbana, IL
5Independent Study Program, University of Illinois College of Medicine Chicago, IL
*Correspondence to: Dr. Keith W. Kelley, University of Illinois, 162 ASL, 1207 W. Gregory Dr., Urbana, IL 61801.
The oncolytic strain 73-T of Newcastle disease virus (NDV) has been reported to be beneficial in the treatment of cancer patients, but little is known about its mechanism of action. In this study, NDV strain 73-T and a wild-type isolate of NDV were found to be potent inducers of tumor necrosis factor (TNF) production by both human peripheral blood mononuclear cells (PBMCs) and rat splenocytes. Antibody inhibition experiments identified TNF-
as the major species of TNF induced by NDV in PBMCs. The effect of recombinant human TNF- (rHuTNF-) on human cancer cells was then examined. Neither rHuTNF- nor supernatants from NDV-stimulated PBMCs were cytotoxic toward the TNF-resistant human malignant melanoma cell line MEL-14. However, when MEL-14 cells were treated with NDV strain 73-T, both rHuTNF- and supernatants from NDV-stimulated PBMCs killed 48% and 55%, respectively, of these tumor cells. Treatment with NDV also conferred TNF susceptibility to the TNF-resistant human malignant melanoma cell line MEL-21 and the human myelogenous leukemia cell line K562. In contrast to its enhanced cytotoxicity toward NDV-treated cancer cells, rHuTNF- had no effect on NDV-treated normal human PBMCs proliferating in response to concanavalin A. These results suggest two important mechanisms for the antineoplastic activity of NDV: (a) induction of TNF- secretion by human PBMCs and (b) enhancement of the sensitivity of neoplastic cells to the cytolytic effects of TNF-.
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