Advertisement

Newcastle Disease Virus: A Promising Vector for Viral Therapy, Immune Therapy, and Gene Therapy of Cancer

  • Volker SchirrmacherEmail author
  • Philippe Fournier
Protocol
Part of the Methods in Molecular Biology™ book series (MIMB, volume 542)

Summary

This review deals with the avian paramyxovirus Newcastle disease virus (NDV) and describes properties that explain its oncolytic activity, its tumor-selective replication behavior, and its immune-stimulatory capacity with human cells. The strong interferon response of normal cells upon contact with NDV appears to be the basis for the good tolerability of the virus in cancer patients and for its immune stimulatory properties, whereas the weak interferon response of tumor cells explains the tumor selectivity of replication and oncolysis. Various concepts for the use of this virus for cancer treatment are pointed out and results from clinical studies are summarized. Reverse genetics technology has made it possible recently to clone the genome and to introduce new foreign genes thus generating new recombinant viruses. These can, in the future, be used to transfer new therapeutic genes into tumors and also to immunize against new emerging pathogens. The modular nature of gene transcription, the undetectable rate of recombination, and the lack of a DNA phase in the replication cycle make NDV a suitable candidate for the rational design of a safe and stable vaccine and gene therapy vector.

Key Words

Immune modulation oncolysis tumor selectivity tumor vaccine 

Notes

Acknowledgment

The work done by our group around Professor Schirrmacher would have not been possible without the dedicated help and contributions of many basic scientists and clinicians. Their names can be obtained from the list of the quoted references.

References

  1. 1.
    Aghi M. and Martzua R.L. (2005). Oncolytic viral therapies—the clinical experience. Oncogene 24: 7802–7815.PubMedCrossRefGoogle Scholar
  2. 2.
    Chlichlia K., Schirrmacher V. and Sandaltzopoulos R. (2005). Cancer immunotherapy: battling tumors with gene vaccines. Curr. Med. Chem. Anti-inflammatory Anti-allergy Agents 4: 353–365.CrossRefGoogle Scholar
  3. 3.
    Schirrmacher V. (2005). T cell mediated immunotherapy of Metastases: State of the art in (2005). Expert Opin. Biol. Ther. 4 (8): 1051–1068.CrossRefGoogle Scholar
  4. 4.
    Sinkovics J. and Horvatz J. (1993) New developments in the virus therapy of cancer: a historical review. Intervirology 36: 193–214.PubMedGoogle Scholar
  5. 5.
    Asada T. (1974) Treatment of human cancer with mumps virus. Cancer 34 (6):1907–1928.PubMedCrossRefGoogle Scholar
  6. 6.
    Shimizu Y., Hasumi K., Okudaira Y., Yamanishi K. and Takahashi M. (1988). Immunotherapy of advanced gynecologic cancer patients utilizing mumps virus. Cancer Detect. Prev. 12: 487–495.PubMedGoogle Scholar
  7. 7.
    Csatary L.K., Eckhard S., Bukosza I., Czegledi F., Fenyvesi. C., Gergely P., Bodey B. and Csatary C.M. (1993) Attenuated veterinary virus vaccine for the treatment of cancer. Cancer Detect. Prev. 17: 6 19–627.Google Scholar
  8. 8.
    Reichard M.W., Lorence, R.M. and Cascino C.J. (1992) Newcastle disease virus selectively kills human tumor cells. J. Surg. Res. 52: 448–453.PubMedCrossRefGoogle Scholar
  9. 9.
    Sinkovics J.G. (1991) Viral oncolysates as human cancer vaccines. Int. Rev. Immunol. 7: 259–287.PubMedCrossRefGoogle Scholar
  10. 10.
    Schirrmacher V., Ahlert I., Heicappell R., Appelhans B. and Von Hoegen P. (1986) Successful application of non-oncogenic viruses for antimetastatic cancer immunotherapy. Cancer Rev. 5:19–49.Google Scholar
  11. 11.
    Heicappell R., Schirrmacher V., von Hoegen P., Ahlert T. and Appelhans B. (1986). Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. I: parameters for optimal therapeutic effects. Int. J. Cancer 37: 569–577.PubMedCrossRefGoogle Scholar
  12. 12.
    Lorence, R.M., Reichard K.W., Katubig B.B., Reyes H.M., Phuangsab H., Mitchell B. R., Cascino J., Walter R.J. and Peeples M.E. (1994) Complete regression of human neuroblastoma xenografts in athymic mice after local Newcastle disease virus therapy. J. Ntl Cancer Inst. (Bethesda) 86: 1228–1233.Google Scholar
  13. 13.
    Umansky V., Shatrov V.A., Lehmann V. and Schirrmacher V. (1996) Induction of NO synthesis in macrophages by Newcastle disease virus is associated with activation of nuclear factor-kappa B. Int. Immunol. 8 (4): 491–498.PubMedCrossRefGoogle Scholar
  14. 14.
    Cassel W.A. and Murray D.R. (1992) 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.PubMedGoogle Scholar
  15. 15.
    Russell S.J. (2002) RNA viruses as virotherapy agents. Cancer Gene Ther. 9: 961–966.PubMedCrossRefGoogle Scholar
  16. 16.
    Stoidl D.F., Lichty B., Knowles S., Marius R., Atkins H., Sonenberg N. and Bell J. (2000) Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nature Med. 6 (7): 821–825.CrossRefGoogle Scholar
  17. 17.
    Kasuya H., Takeda S., Shimoyama S., Shikano T., Nomura N., Kanazumi N., Nomoto S., Sugimoto H. and Nakao A. (2007) Oncolytic virus therapy—foreword. Curr Cancer Drug Targets 7 (2): 123–125.PubMedCrossRefGoogle Scholar
  18. 18.
    Alexander D.J. (1997). Newcastle disease and other Paramyxoviridae infections. In: Diseases of Poultry (Calnek, B.W., Barnes H.J., Beard C.W., McDougald L. and Saif J.Y.M. eds.), 10th ed. Lowa State University, Ames, IA, pp. 541–569.Google Scholar
  19. 19.
    Lorence R.M., Roberts M.S., Groene W.S. and Rabin H. (2003) Replication-competent, oncolytic Newcastle disease virus for cancer therapy. In: Replication-Competent Viruses for Cancer Therapy. (Hernaiz Driever P., Rabkin S.D., eds.), Collection: Monographs in Virology Basel, Karger, vol. 22, pp. 160–182.Google Scholar
  20. 20.
    Alexander D.J. (1988) Historical aspects. In: Newcastle Disease. (Alexander D.J. (ed.) Kluwer, Boston, pp. 1–10.CrossRefGoogle Scholar
  21. 21.
    Doyle T.M. (1927) A hitherto unrecorded disease of fowls due to a filter-passing virus. J Comp Pathol Ther 40: 144–169.Google Scholar
  22. 22.
    de Leeuw O. and Peeters B. (1999) Complete nucleotide sequence of Newcastle disease virus: evidence for the existence of a new genus within the subfamily Paramyxovirinae. J. Gen. Virol. 80 (Pt 1): 131–136.PubMedGoogle Scholar
  23. 23.
    Lamb RA., Parks G.D. (2007) Paramyxoviridae: their viruses and their replication. In Fields Virology. Fifth edition. (Knipe D.M. and Howley P.M. eds). Wolters Kluwer /Lippincott Williams & Wilkins, pp. 1449–1496.Google Scholar
  24. 24.
    Wheelock E.F., Dingle J.H. (1964) Observations on the repeated administration of viruses to a patient with acute leukaemia. A preliminary report. N. Engl. J. Med. 24: 271:645–651.CrossRefGoogle Scholar
  25. 25.
    Cassel W.A., Garrett R.E. (1965) Newcastle Disease Virus as an antineoplastic agent. Cancer. 18: 863–868.PubMedCrossRefGoogle Scholar
  26. 26.
    Csatary L.K. (1971) Viruses in the treatment of cancer. Lancet 2 (7728): 825.PubMedCrossRefGoogle Scholar
  27. 27.
    Sinkovics J.G., Horvath J.C. (eds) (2005) Viral therapy of cancer, Marcel Dekker, New York.Google Scholar
  28. 28.
  29. 29.
    Sinkovics J.G. and Horvath J.C. (2000). Newcastle Disease Viurs (NDV): brief history of its oncolytic strains. J. Clin. Virol. 16 (1): 1–15.PubMedCrossRefGoogle Scholar
  30. 30.
    Schirrmacher V., Haas C., Bonifer R., Ahlert T., Gerhards R. and Ertel C. (1999). 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: 63–73.PubMedCrossRefGoogle Scholar
  31. 31.
    Janke M., Peeters B., de Leeuw O., Moorman R., Arnold A., Fournier P., Schirrmacher V. (2007). Recombinant Newcastle Disease Virus (NDV) with inserted gene coding for GM-CSF as a new vector for cancer immunogene therapy. Gene Ther. 14(23): 1639–1649.PubMedCrossRefGoogle Scholar
  32. 32.
    DiNapoli J.M., Kotelkin A., Yang L., Elankumaran S., Murphy B.R., Samal S.K., Collins P.L. and Bukreyev A. (2007). Newcastle Disease Virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens. Proc. Natl. Acad. Sci. USA 104 (23): 9788–9793.PubMedCrossRefGoogle Scholar
  33. 33.
    Nagai Y., Hamaguchi M., Toyoda T. (1989) Molecular biology of Newcastle disease virus. Prog Vet Microbiol Immunol. 5: 16–64.PubMedGoogle Scholar
  34. 34.
    Yusoff K., Tan W.S. (2001) Newcastle disease virus: macromolecules and opportunities. Avian Pathol. 30: 439–455.PubMedCrossRefGoogle Scholar
  35. 35.
    Calain P., Roux L. (1993) The rule of six, a basic feature for efficient replication of Sendai virus defective interfering RNA. J. Virol. 67 (8): 4822–4830.PubMedGoogle Scholar
  36. 36.
    Peeters B.P., Gruijthuijsen Y.K., de Leeuw O.S., Gielkens A.L. (2000) Genome replication of Newcastle disease virus: involvement of the rule-of-six. Arch. Virol. 145 (9): 1829–1845.PubMedCrossRefGoogle Scholar
  37. 37.
    Lamb R.A., Paterson R.G., Jardetzky T.S. (2006) Paramyxovirus membrane fusion: lessons from the F and HN atomic structures. Virology 344 (1): 30–37.PubMedCrossRefGoogle Scholar
  38. 38.
    Suzuki Y., Suzuki T., Matsunaga M., Matsumoto M..J. (1985) Gangliosides as paramyxovirus receptor. Structural requirement of sialo-oligosaccharides in receptors for hemagglutinating virus of Japan (Sendai virus) and Newcastle disease virus. Biochem (Tokyo) 97 (4): 1189–1199.Google Scholar
  39. 39.
    Ferreira L., Villar E. and Munoz-Barroso I. (2004). Gangliosides and N-glycoproteins function as Newcastle Disease Virus receptors. Int. J. Biochem. Cell Biol. 36: 2344–2356.PubMedCrossRefGoogle Scholar
  40. 40.
    Villar E. and Barroso I.M. (2006) Role of sialic acid-containing molecules in paramyxovirus entry into the host cell: a minireview. Glycoconj J. 23 (1–2): 5–17.PubMedCrossRefGoogle Scholar
  41. 41.
    Cantin C., Holguera J., Ferreira L., Villar E. and Munoz-Barroso I. (2007). Newcastle Disease Virus may enter cells by caveolae-mediated endocytosis. J. Gen. Virol. 88: 559–569.PubMedCrossRefGoogle Scholar
  42. 42.
    Laliberte J.P., McGinnes L.W., Peeples M.E., Morrison T.G. (2006). Integrity of membrane lipid rafts is necessary for the ordered assembly and release of infectious Newcastle Disease Virus particles. J. Virol. 80 (21): 10652–10662.PubMedCrossRefGoogle Scholar
  43. 43.
    Pantua H.D., McGinnes L.W., Peeples M.E., Morrison T.G. (2006). Requirements for the assembly and release of Newcastle Disease Virus-like particles. J. Virol. 80 (22): 11062–11075.PubMedCrossRefGoogle Scholar
  44. 44.
    Fournier P., Zeng J. and Schirrmacher V. (2003). Two ways to induce innate immune responses in human PBMCs: Paracrine stimulation of IFN-α responses by viral protein or dsRNA. Int. J. Oncol. 23: 673–680.PubMedGoogle Scholar
  45. 45.
    Taniguchi T. and Takaoka A. (2002). The interferon-alpha/beta system in antiviral responses: a multimodal machinery of gene regulation by the IRF family of transcription factors. Curr. Opin. Immunol. 14: 111–116.PubMedCrossRefGoogle Scholar
  46. 46.
    Sadler A.J. and Williams B.R. (2007) Structure and function of the protein kinase R. Curr Top Microbiol Immunol. 316: 253–292.PubMedCrossRefGoogle Scholar
  47. 47.
    Fiola C., Peeters B., Fournier P., Arnold A., Bucur M. and Schirrmacher V. (2006) Tumor selective replication of Newcastle Disease Virus: association with defects of tumor cells in antiviral defence. Int. J. Cancer 15, 119 (2): 328–338.CrossRefGoogle Scholar
  48. 48.
    Haller O., Kochs G. and Weber F. (2007) Interferon, Mx, and viral countermeasures. Cytokine Growth Factor Rev. 18 (5–6): 425–433.PubMedCrossRefGoogle Scholar
  49. 49.
    Malathi K., Dong B., Gale M. and Silverman R.H. (2007) Small self-RNA generated by RNase L amplifies antiviral innate immunity. Nature 446: 816–819.CrossRefGoogle Scholar
  50. 50.
    Ahlert T., Schirrmacher V. (1990) Isolation of a human melanoma adapted Newcastle disease virus mutant with highly selective replication patterns. Cancer Res. 50 (18): 5962–5968.PubMedGoogle Scholar
  51. 51.
    Fábián U., Csatary C., Szeberényi J. and Csatary L.K. (2007). p53-independent endoplasmic reticulum stress-mediated cytotoxicity of a Newcastle Disease Virus strain in tumor cell lines. J. Virol. 81 (6): 2817–2830.PubMedCrossRefGoogle Scholar
  52. 52.
    Elankumaran S., Rockemann D. and Samal S.K. (2006). Newcastle Disease Virus exerts oncolysis by both intrinsic and extrinsic caspase-dependent pathways of cell death. J. Virol. 80 (15): 7522–7534.PubMedCrossRefGoogle Scholar
  53. 53.
    Liu T.C. and Kirn D. (2007) Systemic efficacy with oncolytic virus therapeutics: clinical proof-of-concept and future directions. Cancer Res. 67 (2): 429–432.PubMedCrossRefGoogle Scholar
  54. 54.
    Apostolidis L., Schirrmacher V. and Fournier P. (2007). Host mediated anti-tumor effect of oncolytic Newcastle Disease Virus after locoregional application. Int. J. Oncol. 31: 1009–1019.PubMedGoogle Scholar
  55. 55.
    Ito Y., Nagai Y. and Maeno K. (1982) Interferon production in mouse spleen cells and mouse fibroblasts (L cells) stimulated by various strains of Newcastle disease virus. J. Gen. Virol. 62 (Pt 2): 349–352.PubMedCrossRefGoogle Scholar
  56. 56.
    Lorence R.M., Rood P.A. and Kelley K.W. (1988) Newcastle disease virus as an antineoplastic agent: induction of tumor necrosis factor-alpha and augmentation of its cytotoxicity. J. Natl. Cancer Inst. 80 (16): 1305–1312.PubMedCrossRefGoogle Scholar
  57. 57.
    Aigner M., Fournier P. and Schirrmacher V. (2007) An effective tumor vaccine with optimized costimulation via bi- and trispecific fusion proteins. Int. J. Oncol. (in press).Google Scholar
  58. 58.
    Sato K., Hida S., Takayanagi H., Yokochi T., Kayagaki N., Takeda K., Yagita H., Okumura K., Tanaka N., Taniguchi T. and Ogasawara K. (2001) Antiviral response by natural killer cells through TRAIL gene induction by IFN-α/β. Eur. J. Immunol. 31: 31–38.CrossRefGoogle Scholar
  59. 59.
    Schirrmacher V., Bai L., Umansky V., Yu L., Xing Y. and Qian Z. (2000). Newcastle Disease Virus activates macrophages for antitumor activity. Int. J. Oncol. 16: 363–373.PubMedGoogle Scholar
  60. 60.
    Umansky V., Shatrov V.A., Lehmann V. and Schirrmacher V. (1996). Induction of nitric oxide synthesis in macrophages by Newcastle Disease Virus is associated with activation of nuclear factor-B. Int. Immunol., 8 (4): 491–498.PubMedCrossRefGoogle Scholar
  61. 61.
    Washburn B., Weigand M.A., Grosse-Wilde A., Janke M., Stahl H., Rieser E., Sprick M.R., Schirrmacher V. and Walczak H. (2003). TNF-related apoptosis-inducing ligand mediates tumoricidal activity of human monocytes stimulated by Newcastle Disease Virus. J. Immun. 170 (4): 1814–1821.PubMedGoogle Scholar
  62. 62.
    Cella M., Salio M., Sakakibara Y., Langen H., Julkunen I. and Lanzavecchia A. (1999) Maturation, activation and protection of dendritic cells induced by double-stranded RNA. J. Exp. Med. 189: 821–829.PubMedCrossRefGoogle Scholar
  63. 63.
    Bai L., Koopmann J., Fiola C., Fournier P. and Schirrmacher V. (2002). Dendritic cells pulsed with viral oncolysates potently stimulate autologous T cells from cancer patients. Int. J. Oncol. 21: 685–694.PubMedGoogle Scholar
  64. 64.
    Lodolce J.P., Burkett P.R., Boone D.L., Chien M., Ma A. (2001) T cell-independent interleukin 15Ralpha signals are required for bystander proliferation. J. Exp. Med. 194 (8):1187–1194.PubMedCrossRefGoogle Scholar
  65. 65.
    Dubsky P., Saito H., Leogier M., Dantin C., Connolly J.E., Banchereau J., Palucka A.K. (2007) IL-15-induced human DC efficiently prime melanoma-specific naive CD8 + T cells to differentiate into CTL.Eur J Immunol. 37 (6): 1678–1690.PubMedCrossRefGoogle Scholar
  66. 66.
    Von Hoegen P., Weber E. and Schirrmacher V. (1988) Modification of tumor cells by a low dose of Newcastle Disease Virus; augmentation of the tumor-specific T cell response in the absence of an anti-viral response. Eur. J. Immunology 18: 1159–1166.CrossRefGoogle Scholar
  67. 67.
    Schild H.J., von Hoegen P. and Schirrmacher V. (1988). Modification of tumor cells by a low dose of Newcastle Disease Virus: II. Augmented tumor specific T cell response as a result of CD4 + and CD8 + immune T cell cooperation. Cancer Immunol. Immunother, 28: 22–28.Google Scholar
  68. 68.
    Von Hoegen P., Heicappell R., Griesbach A., Altevogt P. and Schirrmacher V. (1988). Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. III. Postoperative activation of tumor-specific CTLP from mice with metastases requires stimulation with the specific antigen plus additional signals. Proc. 8th Sapporo Cancer Seminar Invasion & Metastasis 9: 117–133.Google Scholar
  69. 69.
    Ertel C., Millar N.S., Emmerson P.T., Schirrmacher V. and von Hoegen P. (1993). Viral hemagglutinin augments peptide specific cytotoxic T-cell responses. Eur. J. Immunol. 23: 2592–2596.PubMedCrossRefGoogle Scholar
  70. 70.
    Termeer C.C., Schirrmacher V., Bröcker E.B. and Becker J.C. (2000) Newcastle-Disease-Virus infection induces a B7–1/ B7–2 independent T-cell-costimulatory activity in human melanoma cells. Cancer Gene Ther. 7 (2): 316–323.PubMedCrossRefGoogle Scholar
  71. 71.
    Haas C., Ertel C., Gerhards R. and Schirrmacher V. (1998) Introduction of adhesive and costimulatory immune functions into tumor cells by infection with Newcastle Disease Virus. Int. J. Oncol. 13: 1105–1115.PubMedGoogle Scholar
  72. 72.
    Washburn B. and Schirrmacher V. (2002) Human tumor cell infection by Newcastle Disease Virus leads to upregulation of HLA and cell adhesion molecules and to induction of interferons, chemokines and finally apoptosis. Int. J. Oncol. 21 (1): 85–93.PubMedGoogle Scholar
  73. 73.
    Takeda K., Kaisho T. and Akira S. (2003) Toll-like receptors. Annu Rev Immunol. 21: 335–76.PubMedCrossRefGoogle Scholar
  74. 74.
    Thompson AJ and Locarnini SA. (2007) Toll-like receptors, RIG-I-like RNA helicases and the antiviral innate immune response. Immunol. Cell. Biol. 85(6):435–445.PubMedCrossRefGoogle Scholar
  75. 75.
    Kato H., Sato S., Yoneyama M., Yamamoto M., Uematsu S., Matsui K., Tsujimura T., Takeda K., Fujita T., Takeuchi O. and Akira S. (2005) Cell type-specific involvement of RIG-I in antiviral response. Immunity 23 (1): 19–28.PubMedCrossRefGoogle Scholar
  76. 76.
    Melchjorsen J., Jensen S.B., Malmgaard L., Rasmussen S.B., Weber F., Bowie A.G., Matikainen S., Paludan S.R. (2005) Activation of innate defense against a paramyxovirus is mediated by RIG-I and TLR7 and TLR8 in a cell-type-specific manner. J. Virol. 79 (20): 12944–12951.PubMedCrossRefGoogle Scholar
  77. 77.
    Magyarics Z., Rajnavölgyi E. (2005) Professional type I interferon-producing cells—a unique subpopulation of dendritic cells. Acta Microbiol Immunol Hung. 52 (3–4): 443–462.PubMedCrossRefGoogle Scholar
  78. 78.
    Kawai T. and Akira S. (2005). Pathogen recognition with Toll-like receptors. Curr. Opin. Immunol. 17: 338–344.PubMedCrossRefGoogle Scholar
  79. 79.
    Schulz O., Diebold S.S., Chen M., Näslund T.I., Nolte M.A., Alexopoulou L., Azuma Y.T., Flavell R.A., Liljeström P., Reis E. and Sousa C. (2005) Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature 433 (7028): 887–892.PubMedCrossRefGoogle Scholar
  80. 80.
    Lindenmann J. (1974) Viruses as immunological adjuvants in cancer. Biochim Biophys Acta 355 (1): 49–75.PubMedGoogle Scholar
  81. 81.
    Kyburz D., Aichele P., Speiser D.E., Hengartner H., Zinkernagel R.M., Pircher H. (1993) T cell immunity after a viral infection versus T cell tolerance induced by soluble viral peptides. Eur. J. Immunol. 23: 1956–1962.PubMedCrossRefGoogle Scholar
  82. 82.
    Sato K., Hida S., Takayanagi H., Yokochi T., Kayagaki N., Takeda K., Yagita H., Okumura K., Tanaka N., Taniguchi T. and Ogasawara K. (2001) Antiviral response by natural killer cells through TRAIL gene induction by IFN-alpha/beta. Eur J Immunol 31: 3138.PubMedCrossRefGoogle Scholar
  83. 83.
    Kumar-Sinha C., Varambally S., Sreekumar A. and Chinnaiyan A.M. (2002) Molecular cross-talk between the TRAIL and interferon signalling pathways. J. Biol. Chem. 277: 575–585.PubMedCrossRefGoogle Scholar
  84. 84.
    Washburn B., Weigand M.A., Grosse-Wilde A., Janke M., Stahl H., Rieser E., Sprick M.R., Schirrmacher V. and Walczak H. (2003) TRAIL mediates tumoricidal activity of human monocytes stimulated by Newcastle Disease Virus. J. Immunol. 170: 1814–1821.PubMedGoogle Scholar
  85. 85.
    Le Bon A., Schiavoni G., D'Agostino G., Gresser I., Belardelli F. and Tough D.F. (2001) Type I interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. Immunity 14 (4): 461–470.PubMedCrossRefGoogle Scholar
  86. 86.
    Matzinger P. (1994) Tolerance, danger, and the extended family. Ann. Rev. Immunol. 12: 991–1045.CrossRefGoogle Scholar
  87. 87.
    Matzinger P. (2002) The danger model: a renewed sense of self. Science 296: 301–305.PubMedCrossRefGoogle Scholar
  88. 88.
    Forden C. (2004) Do T lymphocytes correlate danger signals to antigen? Med Hypotheses. 62 (6): 898–906.PubMedCrossRefGoogle Scholar
  89. 89.
    Goodbourn, L. Didcock and Randall R.E. (2000) Interferons: cell signa, immune modulation, antiviral response and virus countermeasures, J. Gen. Virol. 81: 2341–2364.PubMedGoogle Scholar
  90. 90.
    Hengel U.H., Koszinowski U.H. and Conzelmann K.K. (2005) Viruses know it all new insights into IFN networks, Trends Immunol. 26: 396–401.PubMedCrossRefGoogle Scholar
  91. 91.
    Yoneyama M., Kikuchi M., Natsukawa T., Shinobu N., Imaizumi T., Biyagishi M, Taira K., Akira S. and Fujita T. (2004) The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat. Immunol. 5: 730–737.PubMedCrossRefGoogle Scholar
  92. 92.
    Gitlin L., Barchet W., Gilfillan S., Cella M., Beutler B., Flavell R.A., Diamond M.S. and Colonna M. (2006) Essential role of MDA-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus. Proc. Natl. Acad. Sci. USA. 103 (22): 8459–8464.PubMedCrossRefGoogle Scholar
  93. 93.
    Hornung V., Ellegast J., Kim S., Brzózka K., Jung A., Kato H., Poeck H., Akira S., Conzelmann K.K., Schlee M., Endres S. and Hartmann G. (2006) 5'′-Triphosphate RNA is the ligand for RIG-I. Science. 314 (5801): 994–997.PubMedCrossRefGoogle Scholar
  94. 94.
    Bowie A.G. and Fitzgerald K.A. (2007) RIG-I: tri-ing to discriminate between self and non-self RNA. Trends Immunol. 28 (4): 147–150.PubMedCrossRefGoogle Scholar
  95. 95.
    Servant M.J., Tenoever B. and Lin R. (2002) Overlapping and distinct mechanisms regulating IRF-3 and IRF-7 function. J Interferon Cytokine Res. 22 (1): 49–58.PubMedCrossRefGoogle Scholar
  96. 96.
    Levy D.E., Marié I., Smith E. and Prakash A. (2002) Enhancement and diversification of IFN induction by IRF-7-mediated positive feedback. J. Interferon Cytokine Res. 22 (1): 87–93.PubMedCrossRefGoogle Scholar
  97. 97.
    Von Hoegen P., Zawatzky R. and Schirrmacher V. (1990) 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 alfa, beta. Cellular Immunology 126: 80–90.PubMedCrossRefGoogle Scholar
  98. 98.
    Zeng J., Fournier P. and Schirrmacher V. (2002) Induction of interferon and tumor necrosis factor-related apoptosis-inducing blood mononuclear cells by hemagglutinin-neuraminidase but not F protein of Newcastle Disease Virus. Virology, 297: 19–30.PubMedCrossRefGoogle Scholar
  99. 99.
    Rogge L., Barberis-Maino L., Biffi M., Passini N., Presky D.H., Gubler Sinigaglia E. (1997) Selective expression of an interleukin-12 receptor component by human T helper 1 cells. J. Exp. Med. 185: 825.PubMedCrossRefGoogle Scholar
  100. 100.
    Zeng, J., Fournier, P., Schirrmacher, V (2002) Stimulation of human natural interferon- response via paramyxo-virus hemagglutinin lectin-cell interaction. J. Mol. Med. 80: 443–451.PubMedCrossRefGoogle Scholar
  101. 101.
    Fournier P., Zeng J., Von der Lieth C.W., Washburn B., Ahlert T. and Schirrmacher V. (2004) Importance of serine 200 for functional activities of the hemagglutinin-neuraminidase protein of Newcastle Disease Virus. Int. J. Oncol. 24: 623–634.PubMedGoogle Scholar
  102. 102.
    LeBon A. and Tough D.F. (2002) Links between innate and adaptive immunity via type I interferon. Curr. Opin. Immunol. 14: 432–426.CrossRefGoogle Scholar
  103. 103.
    Tough D.F. (2004) Type I interferon as a link between innate and adaptive immunity through dendritic cell stimulation. Leuk. Lymphoma. 45 (2): 257–264.PubMedCrossRefGoogle Scholar
  104. 104.
    Gallucci S. and Matzinger P. (2001) Danger signals: SOS to the immune system. Curr. Opin. Immunol. 13: 114.PubMedCrossRefGoogle Scholar
  105. 105.
    Bian H., Wilden H., Fournier P., Peeters B. and Schirrmacher V. (2006) In vivo efficacy of systemic tumor targeting of a viral RNA vector with oncolytic properties using a bispecific adapter protein. Int. J. Oncol. 29: 1359–1369.PubMedGoogle Scholar
  106. 106.
    Schirrmacher V. and Fournier P. (2006) Newcastle Disease Virus: a promising vector for viral therapy of cancer. In: Viral Therapy of Cancer, (Harrington KJ, Pandha HS and Vile RG eds) Wiley, New York (in press).Google Scholar
  107. 107.
    Lorence R.M., Roberts M.S., O'Neil J.D., Groene W.S., Miller J.A., Mueller S.N. and Bamat M.K. (2007) Phase 1 clinical experience using intravenous administration of PV701, an oncolytic Newcastle disease virus. Curr. Cancer Drug Targets. 7 (2): 157–167.PubMedCrossRefGoogle Scholar
  108. 108.
    Freeman A.I., Zakay-Rones Z., Gomori J.M., Linetsky E., Rasooly L., Greenbaum E., Rozenman-Yair S., Panet A., Libson E., Irving C.S., Galun E. and Siegal T. (2006) Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme. Mol Ther. 13 (1): 221–228.PubMedCrossRefGoogle Scholar
  109. 109.
    Pecora A.L., Rizvi N., Cohen G.I., Meropol N.J., Sterman D., Marshall J.L., Goldberg S., Gorss P., O'Neil J.D., Groene W.S., Roberts M.S., Rabin H., Bamat M.K. and Lorence R.M. (2002). Phase I trial of intravenous administration of PV 701, an oncolytic virus, in patients with advanced solid cancers. J. Clin. Oncol. 20 (9): 2251–2266.PubMedCrossRefGoogle Scholar
  110. 110.
    Hotte S.J., Lorence R.M., Hirte H.W., Polawski S.R., Bamat M.K., O'Neil J.D., Roberts M.S., Groene W.S. and Major P.P. (2007) An optimized clinical regimen for the oncolytic virus PV701. Clin. Cancer Res. 13 (3): 977–985.PubMedCrossRefGoogle Scholar
  111. 111.
    Laurie S.A., Bell J.C., Atkins H.L., Roach J., Bamat M.K., O'Neil J.D., Roberts M.S., Groene W.S. and Lorence R.M. (2006) A phase 1 clinical study of intravenous administration of PV701, an oncolytic virus, using two-step desensitization. Clin. Cancer Res. 12 (8): 2555–2562.PubMedCrossRefGoogle Scholar
  112. 112.
    Czegledi A., Wehmann E. and Lomniczi B. (2003). On the origins and relationships of Newcastle disease virus vaccine strains Hertfordshire and Mukteswar, and virulent strain Herts'33. Avian Pathol. 32: 271–276.PubMedCrossRefGoogle Scholar
  113. 113.
    Csatary L.K., Moss R.W., Beuth J., Töröcsik B., Szeberenyi J. and Bakacs T. (1999) Beneficial treatment of patients with advanced cancer using a Newcastle disease virus vaccine (MTH-68/H). Anticancer Res. 19 (1B): 635–638.PubMedGoogle Scholar
  114. 114.
    Csatary L.K. and Bakács T. (1999) Use of Newcastle disease virus vaccine (MTH-68/H) in a patient with high-grade glioblastoma. JAMA 281 (17): 1588–1589.PubMedCrossRefGoogle Scholar
  115. 115.
    Csatary L.K., Csatary C., Gosztonyi G. and Bodey B. (2006). Promising MTH-68/H Oncolytic Newcastle Disease Virus therapy in human high grade gliomas. Chapter IV In: Focus on Brain Cancer Research (Andrew V. Yang, ed.), Nova Science Publishers New York, pp. 69–82.Google Scholar
  116. 116.
    Csatary L.K., Eckhardt S., Bukosza I., Czegledi F., Fenyvesi C., Gergely P., Bodey B. and Csatary C.M. (1993) Attenuated veterinary virus vaccine for the treatment of cancer. Cancer Detect. Prev. 17 (6): 619–627.PubMedGoogle Scholar
  117. 117.
    Position of the Scientific council on the antitumor studies conducted in Hungary on the Newcastle Disease Virus. (1998) Orv. Hetil. 139: 2903–2905.Google Scholar
  118. 118.
    Nelson N.J. (1999) Scientific interest in Newcastle Disease Virus is reviving. J. Natl. Cancer Inst. 91: 1708–1710.PubMedCrossRefGoogle Scholar
  119. 119.
    Miller L.T. and Yates V.J. (1971) Reactions of human sera to avian adenoviruses and Newcastle disease virus. Avian Dis. 15(4): 781–788.PubMedCrossRefGoogle Scholar
  120. 120.
    Charan S., Mahajan V.M. and Agarwal L.P. (1981) Newcastle disease virus antibodies in human sera. Indian J. Med. Res. 73: 303–307.PubMedGoogle Scholar
  121. 121.
    Van Pel A., Van der Bruggen P., Coulie P.G., Brichard. V.G., Lethe B., Van den Eynde. B., Uyttenhove C., Renauld. J.C. and Boon T. (1995) Genes coding for tumor antigens recognized by cytolytic T lymphocytes. Immunol. Rev. 145: 229–250.PubMedCrossRefGoogle Scholar
  122. 122.
    Baxevanis C.N. and Papamichail M. (1994) Characterization of the anti-tumor immune response in human cancers and strategies for immunotherapy. Crit. Rev. Oncol. Hematol. 16: 157–179.PubMedCrossRefGoogle Scholar
  123. 123.
    Schirrmacher V., Ahlert T., Pröbstle T., Steiner H.H., Herold-Mende C., Gerhards R., Hagmüller E. and Steiner H.H. (1998) Immunization with virus-modified tumor cells. Semin. Oncol. 25 (6): 677–696.PubMedGoogle Scholar
  124. 124.
    Steiner H.H., Bonsanto M.M., Beckhove P., Brysch M., Schuele-Freyer R., Geletneky K., Kremer P., Golamrheza R., Bauer H., Kunze S., Schirrmacher V. and Herold-Mende C.(2004)Anti-tumor vaccination of patients with glioblastoma multiforme: a pilot study to assess: Feasibility, safety and clinical benefit. J. Clin. Oncology 22 (21): 4272–4281CrossRefGoogle Scholar
  125. 125.
    Gilboa E. (1999) The makings of a tumor rejection antigen. Immunity 11: 263–270PubMedCrossRefGoogle Scholar
  126. 126.
    Coulie P.G., Lehman F., Lethé B., Herman J., Lurquin C., Andrawiss M. and Boon T.(1995)A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma. Proc. Natl. Acad. Sci. USA 92: 7976–7980PubMedCrossRefGoogle Scholar
  127. 127.
    Lupetti R., Pisarra P., Verrecchia A., Farina C., Nicolini G., Anichini A., Bordignon C., Sensi M., Parmiani G. and Traversari C. (1998) Translation of a retained intron in tyrosinase-related protein (TRP) 2 mRNA generates a new cytotoxic T lymphocytes (CTL)-defined and shared human melanoma antigen not expressed in normal cells of the melanocytic lineage. J. Exp. Med. 188: 1005–1010.PubMedCrossRefGoogle Scholar
  128. 128.
    Schirrmacher V. and Heicappell R. (1987). Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. II: establishment of specific systemic anti tumor immunity. Clin. Exp. Metastasis 5: 147–156.PubMedCrossRefGoogle Scholar
  129. 129.
    Plaksin D., Porgador A., Vadai E., Feldman M., Schirrmacher V. and Eisenbach L. (1994) 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.PubMedCrossRefGoogle Scholar
  130. 130.
    Shoham J., Hirsch R., Zakay-Rones Z., Osband M.E. and Brennert H.J. (1990) Augmentation of tumor cell immunogenicity by viruses—an approach to specific immunotherapy of cancer. Nat Immun Cell Growth Regul. 9 (3): 165–172.PubMedGoogle Scholar
  131. 131.
    Key M.E. and Hanna M.G. Jr. (1981) Mechanism of action of BCG-tumor cell vaccines in the generation of systemic tumor immunity. II. Influence of the local inflammatory response on immune reactivity. J. Natl. Cancer Inst. 67 (4): 863–869.PubMedGoogle Scholar
  132. 132.
    Schirrmacher V. (2005) Clinical trials of antitumor vaccination with an autologous tumor cell vaccine modified by virus infection: improvement of patient survival based on improved antitumor immune memory. Cancer Immunol. Immunother. 54: 587–598.PubMedCrossRefGoogle Scholar
  133. 133.
    Schirrmacher V., Haas C., Bonifer R., Ahlert T., Gerhards R. and Ertel C. (1999) 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: 63–73.PubMedCrossRefGoogle Scholar
  134. 134.
    Schirrmacher V., Feuerer M., Fournier P., Ahlert T., Umansky V. and Beckhove P. (2003) T-cell priming in bone marrow: the potential for long-lasting protective anti-tumor immunity. Trends Mol Med. 9 (12): 526–534.PubMedCrossRefGoogle Scholar
  135. 135.
    Schirrmacher V. and von Hoegen P. (1993) Importance of tumor cell membrane integrity and viability for CTL activation by cancer vaccines. Vaccine Res. 2: 183–196Google Scholar
  136. 136.
    Ahlert T., Sauerbrei W., Bastert G., Ruhland S., Bartik B., Simiantonaki N., Schumacher J., Häcker B., Schumacher M. and Schirrmacher V. (1997) Tumor-cell number and viability as quality and efficacy parameters of autologous virus-modified cancer vaccines in patients with breast or ovarian cancer. J Clin Oncol. 15 (4): 1354–1366.PubMedGoogle Scholar
  137. 137.
    Schirrmacher V. (2005) Anti-tumor immune memory and its activation for control of residual tumor cells and improvement of patient survival. In: Virus Therapy of Human Cancers (Sinkovics, J., Horvath, J., eds), Marcel Decker, New York.Google Scholar
  138. 138.
    Lehner B., Schlag P., Liebrich W. and Schirrmacher V. (1990) Postoperative active specific immunization in curatively resected colorectal cancer patients with virus-modified autologous tumor cell vaccine. Cancer Immunol. Immuntherap. 32: 173–178.CrossRefGoogle Scholar
  139. 139.
    Schlag P., Manasterski M., Gerneth Th., Hohenberger P., Dueck M., Herfarth Ch., Liebrich W. and Schirrmacher V. (1992). Active specific Immunotherapy with NDV modified autologous tumor cells following liver metastases resection in colorectal cancer: First evaluation of clinical response of a Phase II trial. Cancer Immunol. Immunother. 35: 325–330.PubMedCrossRefGoogle Scholar
  140. 140.
    Bohle W., Schlag P., Liebrich W., Hohenberger P., Manasterski M., Möller P., and Schirrmacher V. (1990). Postoperative active specific immunization in colorectal cancer patients with virus-modified autologous tumour cell vaccine: first clinical results with tumour cell vaccines modified with live but avirulent Newcastle Disease Virus. Cancer 66: 1517–1523.PubMedCrossRefGoogle Scholar
  141. 141.
    Liebrich W., Schlag P., Manasterski M., Lehner B., Stöhr M. and Möller P., Schirrmacher V. (1991). In vitro and clinical characterization of a Newcastle Disease virus-modified autologous tumor cell vaccine for treatment of colorectal cancer patients. Europ. Journal Cancer 27: 703–710.CrossRefGoogle Scholar
  142. 142.
    Ockert D., Schirrmacher V., Beck N., Stoelben E., Ahlert T., Flechtenmacher J., Hagmüller E., Nagel M. and Saeger H.D. (1996). Newcastle Disease Virus infected intact autologous tumor cell vaccine for adjuvant active specific immunotherapy of resected colorectal carcinoma. Clin. Cancer Res. 2: 21–28.PubMedGoogle Scholar
  143. 143.
    Pomer S., Schirrmacher V., Thiele R., Löhrke H. and Staehler G. (1995). Tumor response and 4 year survival data of patients with advanced renal cell carcinoma treated with autologous tumor vaccine and subcutaneous r-IL-2 and IFN-Alpha 2b. Int. J. Oncol. 6: 947–954.PubMedGoogle Scholar
  144. 144.
    Ahlert T., Sauerbrei W., Bastert G., Ruhland S., Bartik B., Simiantonaki N., Schumacher, J., Häcker B., Schumacher M., and Schirrmacher V. (1997) Tumor cell number and viability as quality and efficacy parameters of autologous virus modified cancer vaccines. J. Clin. Oncol. 15: 1354–1366.PubMedGoogle Scholar
  145. 145.
    Karcher J., Dyckhoff G., Beckhove P., Reisser C., Brysch M., Ziouta Y., Helmke B., Weidauer H., Schirrmacher V. and Herold-Mende C. (2004). Anti-tumor vaccination with HNSCC with autologous virus-modified tumor cells. Cancer Res. 64 (21): 8057–8061.PubMedCrossRefGoogle Scholar
  146. 146.
    Haas C., Lulei M., Fournier P., Arnold A. and Schirrmacher V. (2005) T-cell triggering by CD3- and CD28-binding molecules linked to a human virus-modified tumor cell vaccine. Vaccine 23: 2439–2453.PubMedCrossRefGoogle Scholar
  147. 147.
    Haas C., Lulei M., Fournier P., Arnold A. and Schirrmacher V. (2005) A tumor vaccine containing anti-CD3 and anti-CD28 bispecific antibodies triggers strong and durable anti-tumor activity in human lymphocytes. Int. J. Cancer 118 (3): 658–667.CrossRefGoogle Scholar
  148. 148.
    Bian H., Fournier P., Moormann R., Peeters B. and Schirrmacher V. (2005) Selective gene transfer in vitro to tumor cells via recombinant Newcastle Disease Virus. Cancer Gene Ther. 12: 295–303.PubMedCrossRefGoogle Scholar
  149. 149.
    Bian H., Fournier P., Moormann R., Peeters B. and Schirrmacher V. (2005) Selective gene transfer to tumor cells by recombinant Newcastle Disease Virus via a bispecific fusion protein. Int. J. Oncol. 26: 431–439.PubMedGoogle Scholar
  150. 150.
    Bian H., Fournier P., Peeters B. and Schirrmacher V. (2005) Tumor-targeted gene transfer in vivo via recombinant Newcastle Disease Virus modified by a bispecific fusion protein. Int. J. Oncol. 27: 377–384.PubMedGoogle Scholar
  151. 151.
    Conzelmann K.K. (1998) Nonsegmented negative-strand RNA viruses: genetics and manipulation of viral genomes. Ann. Rev. Genet. 32: 123–162.PubMedCrossRefGoogle Scholar
  152. 152.
    García-Sastre A. (1998) Negative-strand RNA viruses: applications to biotechnology. Trends Biotechnol. 16: 230–235.PubMedCrossRefGoogle Scholar
  153. 153.
    Nagai Y. and Kato A. (1999) Paramyxovirus reverse genetics is coming of age. Microbiol. Immunol. 43: 613–624.PubMedGoogle Scholar
  154. 154.
    Roberts A. and Rose J.K. (1998) Recovery of negative-strand RNA viruses from plasmid DNAs: a positive approach revitalizes a negative field. Virology 247: 1–6.PubMedCrossRefGoogle Scholar
  155. 155.
    Peeters B.P.H., de Leeuw O.S., Koch G. and Gielkens A.L.J. (1999) Rescue of Newcastle disease virus from cloned cDNA: evidence that cleavability of the fusion protein is a major determinant for virulence. J. Virol. 73: 5001–5009.PubMedGoogle Scholar
  156. 156.
    Römer-Oberdörfer A., Mundt E., Mebatsion T., Buchholz U. and Mettenleiter T.C. (1999) Generation of recombinant lentogenic Newcastle disease virus from cDNA. J. Gen. Virol. 80: 2987–2995.PubMedGoogle Scholar
  157. 157.
    Mebatsion T., Verstegen S., De Vaan L.T., Römer-Oberdörfer A. and Schrier C.C. (2001). A recombinant Newcastle Disease Virus with low-level V protein expression is immunogenic and lacks pathogenicity for chicken embryos. J. Virol. 75: 420–428.PubMedCrossRefGoogle Scholar
  158. 158.
    Vigil A., Park M.S., Martinez O., Chua M.A., Xiao S., Cros J.F., Martínez-Sobrido L., Woo S.L. and García-Sastre A. (2007) Use of reverse genetics to enhance the oncolytic properties of Newcastle disease virus. Cancer Res. 67 (17): 8285–8292.PubMedCrossRefGoogle Scholar
  159. 159.
    Zhao H. and Peeters B.P. (2003) Recombinant Newcastle disease virus as a viral vector: effect of genomic location of foreign gene on gene expression and virus replication. J. Gen. Virol. 84 (Pt 4): 781–788.PubMedCrossRefGoogle Scholar
  160. 160.
    Huang Z., Krishnamurthy S., Panda A. and Samal S.K. (2001) High-level expression of a foreign gene from the most 3'′-proximal locus of a recombinant Newcastle disease virus. J. Gen. Virol. 82 (Pt 7): 1729–1736.PubMedGoogle Scholar
  161. 161.
    Nakaya T., Cros J., Park M.S., Nakaya Y., Zheng H., Sagrera A., Villar E., García-Sastre A. and Palese P. (2001) Recombinant Newcastle Disease Virus as a vaccine vector. J. Virol. 75: 11868–11873.PubMedCrossRefGoogle Scholar
  162. 162.
    Bureyev A., Huang Z., Yang L., Elankumaran S., St. Claire M., Murphy B.R., Samal S.K. and Collins P.L. (2005). Recombinant Newcastle Disease Virus expressing a foreign viral antigen is attenuated and highly immunogenic in primates. J. Virol. 79: 13275–13284.CrossRefGoogle Scholar
  163. 163.
    Ge J., Deng G., Wen Z., Guobing T., Wang Y., Shi J., Wang X., Li Y., Hu S., Jiang Y., Yang C., Yu K., Bu Z. and Chen H. (2007). Newcastle Disease Virus-based live attenuated vaccine completely protects chickens and mice from lethal challenge of homologous and heterologous H5N1 avian influenza viruses. J. Virol. 81 (1): 150–158.PubMedCrossRefGoogle Scholar
  164. 164.
    Sivasamugham L.A., Cardosa M.J., Tan W.S. and Yusoff K. (2006) Recombinant Newcastle Disease virus capsids displaying enterovirus 71 VP1 fragment induce a strong immune response in rabbits. J. Med. Virol. 78 (8): 1096–1104.PubMedCrossRefGoogle Scholar
  165. 165.
    Veits J., Wiesner D., Fuchs W., Hoffmann B., Granzow H., Starick E., Mundt E., Schirrmeier H., Mebatsion T., Mettenleiter T.C. and Römer-Oberdörfer A. (2006) Newcastle disease virus expressing H5 hemagglutinin gene protects chickens against Newcastle disease and avian influenza. Proc. Natl. Acad. Sci. USA 103 (21): 8197–8202.PubMedCrossRefGoogle Scholar
  166. 166.
    Huang Z., Elankumaran S., Yunus A.S., Samal S.K. (2004) A recombinant Newcastle disease virus (NDV) expressing VP2 protein of infectious bursal disease virus (IBDV) protects against NDV and IBDV. J. Virol. 78 (18): 10054–10063.PubMedCrossRefGoogle Scholar
  167. 167.
    Alexander D.J. (1988) Newcastle disease virus - an avian paramyxovirus In: Newcastle Disease (Alexander D.J. ed), Kluwer, Boston, pp. 11–22.CrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.German Cancer Research Center, Division of Cellular Immunology D010HeidelbergGermany

Personalised recommendations