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Newcastle Disease Virus (PDQ®)     
Last Modified: 10/08/2009
Health Professional Version
History

The first published report to establish a link between infection with a virus and the regression of cancer appeared in 1912. Reviewed in [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.[7-12] Reviewed in [1,3-6,13-25] 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 1 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. Reviewed in [2,6,15,18,22,25-28]

Cytokines can be directly cytotoxic to virus-infected cells (e.g., tumor necrosis factor [TNF] -alpha Reviewed in [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 Reviewed in [2,29-31]).

As also indicated previously (refer to the General Information 1 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. Reviewed in [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]

Understanding Cancer Series: The Immune System 2.

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: 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: 82-6, 1955. 

  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]

  13. 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]

  14. Kenney S, Pagano JS: Viruses as oncolytic agents: a new age for "therapeutic" viruses? J Natl Cancer Inst 86 (16): 1185-6, 1994.  [PUBMED Abstract]

  15. Kirn DH, McCormick F: Replicating viruses as selective cancer therapeutics. Mol Med Today 2 (12): 519-27, 1996.  [PUBMED Abstract]

  16. 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]

  17. 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]

  18. 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]

  19. Schirrmacher V, Ahlert T, Pröbstle T, et al.: Immunization with virus-modified tumor cells. Semin Oncol 25 (6): 677-96, 1998.  [PUBMED Abstract]

  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]

  21. Schirrmacher V, Haas C, Bonifer R, et al.: Human tumor cell modification by virus infection: an efficient and safe way to produce cancer vaccine with pleiotropic immune stimulatory properties when using Newcastle disease virus. Gene Ther 6 (1): 63-73, 1999.  [PUBMED Abstract]

  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]

  25. Bridgewater J, Collins M: Vaccine immunotherapy for cancer. Mol Cell Biol Hum Dis Ser 5: 140-56, 1995.  [PUBMED Abstract]

  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]

  28. Alberts B, Bray D, Lewis J, et al.: Molecular Biology of the Cell. 3rd ed. New York, NY: Garland Publishing, 1994. 

  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]

  35. Zorn U, Duensing S, Langkopf F, et al.: Active specific immunotherapy of renal cell carcinoma: cellular and humoral immune responses. Cancer Biother Radiopharm 12 (3): 157-65, 1997.  [PUBMED Abstract]

  36. Plaksin D, Porgador A, Vadai E, et al.: Effective anti-metastatic melanoma vaccination with tumor cells transfected with MHC genes and/or infected with Newcastle disease virus (NDV). Int J Cancer 59 (6): 796-801, 1994.  [PUBMED Abstract]

  37. Bier H, Armonat G, Bier J, et al.: Postoperative active-specific immunotherapy of lymph node micrometastasis in a guinea pig tumor model. ORL J Otorhinolaryngol Relat Spec 51 (4): 197-205, 1989.  [PUBMED Abstract]

  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]



Glossary Terms

antibody (AN-tee-BAH-dee)
A protein made by plasma cells (a type of white blood cell) in response to an antigen (a substance that causes the body to make a specific immune response). Each antibody can bind to only one specific antigen. The purpose of this binding is to help destroy the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen.
attenuated
Weakened or thinned. Attenuated strains of disease-causing bacteria and viruses are often used as vaccines. The weakened strains are used as vaccines because they stimulate a protective immune response while causing no disease or only mild disease in the person receiving the vaccine.
B cell
A type of immune cell that makes proteins called antibodies, which bind to microorganisms and other foreign substances, and help fight infections. A B cell is a type of white blood cell. Also called B lymphocyte.
cancer (KAN-ser)
A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.
cervical cancer (SER-vih-kul KAN-ser)
Cancer that forms in tissues of the cervix (the organ connecting the uterus and vagina). It is usually a slow-growing cancer that may not have symptoms but can be found with regular Pap tests (a procedure in which cells are scraped from the cervix and looked at under a microscope). Cervical cancer is almost always caused by human papillomavirus (HPV) infection.
cytokine (SY-toh-kine)
A substance that is made by cells of the immune system. Some cytokines can boost the immune response and others can suppress it. Cytokines can also be made in the laboratory by recombinant DNA technology and used in the treatment of various diseases, including cancer.
cytotoxic (SY-toh-TOK-sik)
Cell-killing.
cytotoxic T cell (SY-toh-TOK-sik ... sel)
A type of immune cell that can kill certain cells, including foreign cells, cancer cells, and cells infected with a virus. Cytotoxic T cells can be separated from other blood cells, grown in the laboratory, and then given to a patient to kill cancer cells. A cytotoxic T cell is a type of white blood cell and a type of lymphocyte. Also called cytotoxic T lymphocyte and killer T cell.
immune system (ih-MYOON SIS-tem)
The complex group of organs and cells that defends the body against infections and other diseases.
infection
Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.
interferon (in-ter-FEER-on)
A biological response modifier (a substance that can improve the body's natural response to infections and other diseases). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and -gamma. The body normally produces these substances. They are also made in the laboratory to treat cancer and other diseases.
natural killer cell (NA-chuh-rul KIH-ler sel)
A type of immune cell that has granules (small particles) with enzymes that can kill tumor cells or cells infected with a virus. A natural killer cell is a type of white blood cell. Also called NK cell and NK-LGL.
Newcastle disease virus (NOO-ka-sul dih-ZEEZ VY-rus)
A bird virus that is being studied in the treatment of cancer. It may be used to kill cancer cells directly, or it may be given as a cancer vaccine to stimulate the body’s immune system. Newcastle disease virus is a type of biological response modifier and vaccine therapy. Also called NDV.
rabies
A disease of the nervous system caused by the rabies virus. Rabies is marked by an increase in saliva production, abnormal behavior, and eventual paralysis and death.
regression
A decrease in the size of a tumor or in the extent of cancer in the body.
tumor necrosis factor (TOO-mer neh-KROH-sis FAK-ter)
A protein made by white blood cells in response to an antigen (substance that causes the immune system to make a specific immune response) or infection. Tumor necrosis factor can also be made in the laboratory. It may boost a person’s immune response, and also may cause necrosis (cell death) of some types of tumor cells. Tumor necrosis factor is being studied in the treatment of some types of cancer. It is a type of cytokine. Also called TNF.
tumor-specific antigen (TOO-mer-speh-SIH-fik AN-tih-jen)
A protein or other molecule that is unique to cancer cells or is much more abundant in them. These molecules are usually found in the plasma (outer) membrane, and they are thought to be potential targets for immunotherapy or other types of anticancer treatment.
vaccine
A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. A vaccine can help the body recognize and destroy cancer cells or microorganisms.
virus (VY-rus)
In medicine, a very simple microorganism that infects cells and may cause disease. Because viruses can multiply only inside infected cells, they are not considered to be alive.


Table of Links

1http://www.cancer.gov/cancertopics/pdq/cam/NDV/HealthProfessional/5.cdr#Section
_5
2http://www.cancer.gov/cancertopics/understandingcancer/immunesystem