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. 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]
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- Cassel WA, Garrett RE: Newcastle disease virus as an antineoplastic agent. Cancer 18 (7): 863-8, 1965.
- 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]
- 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.
- 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]
- Sinkovics JG, Howe CD: Superinfection of tumors with viruses. Experientia 25 (7): 733-4, 1969. [PUBMED Abstract]
- 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]
- Csatary LK, Moss RW, Beuth J, et al.: Beneficial treatment of patients with advanced cancer using a Newcastle disease virus vaccine (MTH-68/H). Anticancer Res 19 (1B): 635-8, 1999 Jan-Feb. [PUBMED Abstract]
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- Lorence RM, Reichard KW, Katubig BB, et al.: Complete regression of human neuroblastoma xenografts in athymic mice after local Newcastle disease virus therapy. J Natl Cancer Inst 86 (16): 1228-33, 1994. [PUBMED Abstract]
- Lorence RM, Katubig BB, Reichard KW, et al.: Complete regression of human fibrosarcoma xenografts after local Newcastle disease virus therapy. Cancer Res 54 (23): 6017-21, 1994. [PUBMED Abstract]
- Reichard KW, Lorence RM, Cascino CJ, et al.: Newcastle disease virus selectively kills human tumor cells. J Surg Res 52 (5): 448-53, 1992. [PUBMED Abstract]
- Schirrmacher V, Ahlert T, Pröbstle T, et al.: Immunization with virus-modified tumor cells. Semin Oncol 25 (6): 677-96, 1998. [PUBMED Abstract]
- 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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- 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]
- 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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