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Newcastle Disease Virus (PDQ®)

  • Last Modified: 04/23/2014

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History

The first published report to establish a link between infection with a virus and the regression of cancer appeared in 1912.[1-6] This report described a woman whose cervical cancer improved following treatment to prevent rabies. The woman had been bitten by a dog, and she was subsequently injected with a vaccine made of attenuated (i.e., weakened) rabies virus. Over the next 60 years, many other viruses, including Newcastle disease virus (NDV), were shown to have anticancer potential.[1,3-25] The first report of positive results using NDV as a treatment for human cancer was published in 1964.[9] By that time, attenuated strains of NDV had been used for almost 2 decades to prevent Newcastle disease in birds, and the inability of this virus to cause serious illness in humans had been established.

As indicated previously (refer to the General Information section of this summary for more information), cells infected with NDV can be killed directly by the virus or indirectly through an immune system response to the infection. The immune system uses a variety of approaches to kill virus-infected cells, including attack by cytotoxic cells (i.e., natural killer cells and/or cytotoxic T cells); attack by antivirus antibodies, which are made by B cells; and the release of cytokines.[2,6,15,18,22,25-28]

Cytokines can be directly cytotoxic to virus-infected cells (e.g., tumor necrosis factor [TNF] -alpha).[14,15,20] In addition, they can stimulate increases in the activity and/or numbers of specific types of immune system cells (e.g., interferon -alpha, interferon-gamma, and TNF-alpha).[2,29-31]

As also indicated previously (refer to the General Information section of this summary for more information), if the immune system is responding to virus-infected cancer cells (or fragments of cancer cells), then better recognition of tumor-specific antigens may occur, and an increased ability to kill uninfected cancer cells may be acquired.[15,18,19,23,26,30,32-38] The immune system would use the same approaches to kill uninfected cancer cells that it uses to kill virus-infected cells. For example, it has been shown that TNF-alpha is directly cytotoxic to some, but not all, cancer cells, whereas normal cells are not harmed by this cytokine.[39-42]

References
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  2. Csatary LK, Eckhardt S, Bukosza I, et al.: Attenuated veterinary virus vaccine for the treatment of cancer. Cancer Detect Prev 17 (6): 619-27, 1993.  [PUBMED Abstract]

  3. Nemunaitis J: Oncolytic viruses yesterday and today. J Oncol Manag 8 (5): 14-24, 1999. 

  4. Webb HE, Smith CE: Viruses in the treatment of cancer. Lancet 1 (7658): 1206-8, 1970.  [PUBMED Abstract]

  5. Ahlert T, Schirrmacher V: Isolation of a human melanoma adapted Newcastle disease virus mutant with highly selective replication patterns. Cancer Res 50 (18): 5962-8, 1990.  [PUBMED Abstract]

  6. Sinkovics J, Horvath J: New developments in the virus therapy of cancer: a historical review. Intervirology 36 (4): 193-214, 1993.  [PUBMED Abstract]

  7. Cassel WA, Garrett RE: Newcastle disease virus as an antineoplastic agent. Cancer 18 (7): 863-8, 1965. 

  8. Eaton MD, Heller JA, Scala AR: Enhancement of lymphoma cell immunogenicity by infection with nononcogenic virus. Cancer Res 33 (12): 3293-8, 1973.  [PUBMED Abstract]

  9. Wheelock EF, Dingle JH: Observations on the repeated administration of viruses to a patient with acute leukemia. A preliminary report. N Engl J Med 271(13): 645-51, 1964. 

  10. Flanagan AD, Love R, Tesar W: Propagation of Newcastle disease virus in Ehrlich ascites cells in vitro and in vivo. Proc Soc Exp Biol Med 90 (1): 82-6, 1955.  [PUBMED Abstract]

  11. Sinkovics JG, Howe CD: Superinfection of tumors with viruses. Experientia 25 (7): 733-4, 1969.  [PUBMED Abstract]

  12. Eaton MD, Levinthal JD, Scala AR: Contribution of antiviral immunity to oncolysis by Newcastle disease virus in a murine lymphoma. J Natl Cancer Inst 39 (6): 1089-97, 1967.  [PUBMED Abstract]

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  20. Lorence RM, Rood PA, Kelley KW: Newcastle disease virus as an antineoplastic agent: induction of tumor necrosis factor-alpha and augmentation of its cytotoxicity. J Natl Cancer Inst 80 (16): 1305-12, 1988.  [PUBMED Abstract]

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  22. Sinkovics JG, Horvath JC: Newcastle disease virus (NDV): brief history of its oncolytic strains. J Clin Virol 16 (1): 1-15, 2000.  [PUBMED Abstract]

  23. Shoham J, Hirsch R, Zakay-Rones Z, et al.: Augmentation of tumor cell immunogenicity by viruses--an approach to specific immunotherapy of cancer. Nat Immun Cell Growth Regul 9 (3): 165-72, 1990.  [PUBMED Abstract]

  24. Csatary LK: Viruses in the treatment of cancer. Lancet 2 (7728): 825, 1971.  [PUBMED Abstract]

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  26. Schirrmacher V, Ahlert T, Heicappell R, et al.: Successful application of non-oncogenic viruses for antimetastatic cancer immunotherapy. Cancer Rev 5: 19-49, 1986. 

  27. Cooper NR, Nemerow GR: The role of antibody and complement in the control of viral infections. J Invest Dermatol 83 (1 Suppl): 121s-127s, 1984.  [PUBMED Abstract]

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  29. Zorn U, Dallmann I, Grosse J, et al.: Induction of cytokines and cytotoxicity against tumor cells by Newcastle disease virus. Cancer Biother 9 (3): 225-35, 1994 Fall.  [PUBMED Abstract]

  30. DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 5th ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1997. 

  31. von Hoegen P, Zawatzky R, Schirrmacher V: Modification of tumor cells by a low dose of Newcastle disease virus. III. Potentiation of tumor-specific cytolytic T cell activity via induction of interferon-alpha/beta. Cell Immunol 126 (1): 80-90, 1990.  [PUBMED Abstract]

  32. Haas C, Ertel C, Gerhards R, et al.: Introduction of adhesive and costimulatory immune functions into tumor cells by infection with Newcastle Disease Virus. Int J Oncol 13 (6): 1105-15, 1998.  [PUBMED Abstract]

  33. Cassel WA, Murray DR: A ten-year follow-up on stage II malignant melanoma patients treated postsurgically with Newcastle disease virus oncolysate. Med Oncol Tumor Pharmacother 9 (4): 169-71, 1992.  [PUBMED Abstract]

  34. Heicappell R, Schirrmacher V, von Hoegen P, et al.: Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. I. Parameters for optimal therapeutic effects. Int J Cancer 37 (4): 569-77, 1986.  [PUBMED Abstract]

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  38. Nesselhut T: Influence on antigen exposition of tumor cells by membrane active substances and viral infections. Hybridoma 12 (5): 553-7, 1993.  [PUBMED Abstract]

  39. Helson L, Green S, Carswell E, et al.: Effect of tumour necrosis factor on cultured human melanoma cells. Nature 258 (5537): 731-2, 1975.  [PUBMED Abstract]

  40. Haranaka K, Satomi N: Cytotoxic activity of tumor necrosis factor (TNF) on human cancer cells in vitro. Jpn J Exp Med 51 (3): 191-4, 1981.  [PUBMED Abstract]

  41. Sugarman BJ, Aggarwal BB, Hass PE, et al.: Recombinant human tumor necrosis factor-alpha: effects on proliferation of normal and transformed cells in vitro. Science 230 (4728): 943-5, 1985.  [PUBMED Abstract]

  42. Fransen L, Van der Heyden J, Ruysschaert R, et al.: Recombinant tumor necrosis factor: its effect and its synergism with interferon-gamma on a variety of normal and transformed human cell lines. Eur J Cancer Clin Oncol 22 (4): 419-26, 1986.  [PUBMED Abstract]