Skip to main content
Log in

MTH-68/H Oncolytic Viral Treatment in Human High-Grade Gliomas

Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Application of virus therapy to treat human neoplasms has over a three decade history. MTH-68/H, a live attenuated oncolytic viral strain of the Newcastle disease virus, is one of the viruses used in the treatment of different malignancies. Here we report on the administration of MTH-68/H to patients with glioblastoma multiforme, the most common and most aggressive neuroectodermal neoplasm with a poor prognosis, averaging six months to a year. Four cases of advanced high-grade glioma were treated with MTH-68/H after the conventional modalities of anti-neoplastic therapies had failed. This treatment resulted in survival rates of 5–9 years, with each patient still living today. Against all odds, each patient resumed a lifestyle that resembles their previous daily routines and enjoys a good quality of life. Each of these patients has regularly received MTH-68/H as their sole form of onco-therapy for a number of years now without interruption.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Simons JW: The Nemunaitis article reviewed: live viruses in cancer treatment. Oncology 16: 1496–1497, 2002

    Google Scholar 

  2. Bodey B, Bodey B Jr, Siegel SE: Immunophenotypical (IP) differential diagnosis and immunobiology of childhood primary brain tumors. A decade of experience. J Pediatric Hematol Oncol 6: 65–84, 1998

    Google Scholar 

  3. von Deimling A, Louis DN, Wiestler OD: Molecular pathways in the formation of gliomas. Glia 15: 328–338, 1995

    Article  CAS  PubMed  Google Scholar 

  4. Kleihues P, Soylemezoglu F, Schauble B, Scheithauer BW, Burger PC: Histopathology, classification, and grading of gliomas. Glia 15: 211–221, 1995

    Article  CAS  PubMed  Google Scholar 

  5. Katsura S, Susuki J, Wada T: Statistical study of brain tumours in the neurosurgical clinics in Japan. J Neurosurg 16: 570–580, 1959

    CAS  PubMed  Google Scholar 

  6. Cairncross JG: The biology of astrocytoma: lessons learned from chronic myelogenous leukemia-hypothesis. J Neuro-Oncol 5: 99–104, 1987

    CAS  Google Scholar 

  7. Bodey B, Zeltzer PM, Saldivar V, Kemshead J: Immunophenotyping of childhood astrocytomas with a library of monoclonal antibodies. Int J Cancer 45: 1079–1087, 1990

    CAS  PubMed  Google Scholar 

  8. Bullard DE, Gillespie Y, Mahaley MS, Bigner DD: Immunobiology of human gliomas. Semin Oncol 13: 94–109, 1986

    CAS  PubMed  Google Scholar 

  9. Ohgaki K, Schäuble B, zur Hausen A, von Ammon K, Kleihues P: Genetic alterations associated with the evolution and progression of astrocytic brain tumors. Virchow Arch 427: 113–118, 1995

    CAS  Google Scholar 

  10. Bodey B, Gröger AM, Bodey B Jr, Siegel SE, Kaiser HE: Immunocytochemical detection of p53 protein expression in various childhood astrocytoma subtypes: Significance in tumor progression. Anticancer Res 17: 1187–1194, 1997

    CAS  PubMed  Google Scholar 

  11. von Deimling A, von Ammon K, Schoenfeld D, Wiestler OD, Seizinger BR, Louis DN: Subsets of glioblastoma multiforme defined by molecular genetic analysis. Brain Pathol 3: 19–26, 1993

    CAS  PubMed  Google Scholar 

  12. Biernat W, Kleihues P, Yonekawa Y, Ohgaki H: Amplifi-cation and overexpression of MDM2 in primary (de novo) glioblastomas. J Neuropathol Exp Neurol 56: 180–185, 1997

    CAS  PubMed  Google Scholar 

  13. Watanabe K, Tachibana O, Sato K, Yonekawa Y, Kleihues P, Ohgaki H: Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol 6: 217–223, 1996

    CAS  PubMed  Google Scholar 

  14. Watanabe K, Tachibana O, Yonekawa Y, Kleihues P, Ohgaki H: Role of gemistocytes in astrocytoma progression. Lab Invest 76: 277–284, 1997

    CAS  PubMed  Google Scholar 

  15. Pollack IF, Campbell JW, Hamilton RL, Martinez AJ, Bozik ME: Proliferation index as a predictor of prognosis in malignant gliomas of childhood. Cancer 79: 849–856, 1997

    Article  CAS  PubMed  Google Scholar 

  16. Webb HE, Gordon Smith CE: Viruses in the treatment of cancer. Lancet 1: 1206–1208, 1970

    CAS  PubMed  Google Scholar 

  17. Driever PH, Rabkin SD (eds): Replication-Competent Viruses for Cancer Therapy. Monographs in Virology. Vol 22. Karger, Basel, 2001

  18. Nemunaitis J: Live viruses in cancer treatment. Oncology 16: 1483–1492, 2002

    PubMed  Google Scholar 

  19. Nelson NJ: Viruses and cancer. J Natl Cancer Inst 91: 1709, 1999

    CAS  PubMed  Google Scholar 

  20. Cassell WA, Garrett RE: Newcastle disease virus as an antineoplastic agent. Cancer 18: 863–868, 1965

    Google Scholar 

  21. Csatary LK: Viruses in the treatment of cancer. Lancet 2: 825, 1971

    CAS  PubMed  Google Scholar 

  22. Csatary LK, Eckhardt S, Bukosza I, Czegledi F, Fenyvesi C, Gergely P, Bodey B, Csatary CM: Attenuated veterinary virus vaccine for the treatment of cancer. Cancer Detect Prev 17: 619–627, 1993

    CAS  PubMed  Google Scholar 

  23. Csatary LK, Csatary E, Moss RW: Scientific interest in Newcastle disease virus is reviving. J Natl Cancer Inst 92: 493–494, 2000

    Article  CAS  PubMed  Google Scholar 

  24. Csatary LK, Moss RW, Beuth J, Türücsik B, Szeberenyi J, Bakacs T: Beneficial treatment of patients with advanced cancer using a Newcastle disease virus vaccine (MTH-68/H). Anticancer Res 19: 635–638, 1999

    CAS  PubMed  Google Scholar 

  25. Fabian Z, Töröcsik B, Csatary LK, Kiss K, Szeberenyi J: Induction of apoptosis by a Newcastle disease virus vaccine (MTH-68/H) in PC12 rat phaeochromocytoma cells. Anticancer Res 21: 125–136, 2001

    CAS  PubMed  Google Scholar 

  26. Szeberenyi J, Fabian Z, Töröcsik B, Kiss K, Csatary LK: Newcastle disease virus-induced apoptosis in PC12 pheochromocytoma cells. Am J Therap 10(4): 282–288, 2003

    Google Scholar 

  27. Csatary LK, Bakacs T: Use of Newcastle disease virus vaccine (MTH-68/H) in a patient with high-grade glioblastoma. JAMA 281: 1588–1589, 1999

    Article  CAS  PubMed  Google Scholar 

  28. Steiner HH, Herold-Mende Ch, Bonsanto M, Geletneky K, Kunze S: Zur Prognose von Hirntumoren: Epidemiologie, ¨ Uberlebenszeit und klinischer Verlauf. Versicherungsmedizin 50: 173–179, 1998

    CAS  PubMed  Google Scholar 

  29. Chamberlain MC, Kormanik PA: Practical guidelines for the treatment of malignant gliomas.West J Med 168: 114–120, 1998

    CAS  PubMed  Google Scholar 

  30. Puzzilli F, Ruggeri A, Mastronadi L, Di Stefano D, Lunardi D: Long-term survival in cerebral glioblastoma. Case report and critical review of the literature. Tumori 84: 69–74, 1998

    CAS  PubMed  Google Scholar 

  31. Pollak L, Gur R, Walach N, Reif R, Tamir L, Schiffer J: Clinical determinants of long-term survival in patients with glioblastoma multiforme. Tumori 83: 613–617, 1997

    CAS  PubMed  Google Scholar 

  32. Salvati M, Cervoni L, Artico M, Caruso R, Gagliardi FM: Long-term survival in patents with supratentorial glioblastoma. J Neuro-Oncol 36: 61–64, 1998

    Article  CAS  Google Scholar 

  33. Yoshida T, Kawano N, Oka H, Fujii K, Nakazato Y: Clinical cure of glioblastoma – two case reports. Neurol Med Chir (Tokyo) 40: 224–229, 2000

    CAS  Google Scholar 

  34. Klein R, Molenkamp G, Sorensen N, Roggendorf W: Favorable outcome of giant cell glioblastoma in a child. Report of an 11-year survival period. Childs Nerv Syst 14: 288–291, 1998

    Article  CAS  PubMed  Google Scholar 

  35. Meyer-Puttlitz B, Hayashi Y, Wahaa A, Rollbrocker B, Boström J, Wiestler OD, Louis D N, Reifenberger G, von Deimling A: Molecular genetic analysis of giant cell glioblastomas. Am J Pathol 151: 853–857, 1997

    CAS  PubMed  Google Scholar 

  36. Roth W, Weller M: Chemotherapy and immunotherapy of malignant glioma: molecular mechanisms and clinical perspectives. Cell Mol Life Sci 56: 481–506, 1999

    CAS  PubMed  Google Scholar 

  37. Fillmore HL, VanMeter TE, Broaddus WC: Membranetype matrix metalloproteinases (MT-MMPs): expression and function during glioma invasion. J Neuro-Oncol 53: 187–202, 2001

    Article  CAS  Google Scholar 

  38. Hosli P, Sappino AP, de Tribolet N, Dietrich PY: Malignant glioma: should chemotherapy be overthrown by experimental treatments? Ann Oncol 9: 589–600, 1998

    CAS  PubMed  Google Scholar 

  39. Alemany R, Gomez-Manzano C, Balague C, Yung WK, Curiel DT, Kyritsis AP, Fueyo J: Gene therapy for glioblastomas: molecular targets, adenoviral vectors, and oncolytic adenoviruses. Exp Cell Res 252: 1–12, 1999

    Article  CAS  PubMed  Google Scholar 

  40. Burton EC, Prados MD: Malignant gliomas. Curr Treat Options Oncol 1: 459–468, 2000

    CAS  PubMed  Google Scholar 

  41. Markert JM, Gillespie GY, Weichselbaum RR, Roizman B, Whitley RJ: Genetically engineered HSV in the treatment of glioma: a review. Rev Med Virol 10: 17–30, 2000

    Article  CAS  PubMed  Google Scholar 

  42. Mahaley Jr MS, Bigner DD, Dudka LF, Wilds PR, Williams DH, Bouldin TW, Whitaker JN, Bynum JM: Immunobiology of primary intracranial tumors. Part 7: Active immunization of patients with anaplastic glioma cells: a pilot study. J Neurosurg 59: 201–207, 1983

    PubMed  Google Scholar 

  43. Mahaley MS, Gillespie GY, Gillespie RP, Watkins PJ, Bigner DD, Wikstrand CJ, MacQueen JM, Sanfilippo F: Immunobiology of primary intracranial tumors. Part 8: serological responses to active immunization of patients with anaplastic gliomas. J Neurosurg 59: 208–216, 1983

    PubMed  Google Scholar 

  44. Bodey B: Spontaneous regression of neoplasms: new possibilities for immunotherapy. Expert Opin Biol Ther 2: 459–476, 2002

    CAS  PubMed  Google Scholar 

  45. Tunici P, Gianni D, Finocchiaro G: Gene therapy of glioblastomas: from suicide to homicide. Prog Brain Res 132: 711–719, 2001

    CAS  PubMed  Google Scholar 

  46. Schluesener HJ, Meyermann R, Deininger M: Immune responses in glioblastoma: an avenue to effective cancer therapy or a mere epiphenomenon? CTMI 265: 259–267, 2002

    CAS  Google Scholar 

  47. Karpati G, Li H, Nalbantoglu J: Molecular therapy for glioblastoma. Curr Opin Mol Ther 1: 545–552, 1999

    CAS  PubMed  Google Scholar 

  48. Lorence RM, Roberts MS, Groene WS, Rabin H: Replication-competent, oncolytic Newcastle disease virus for cancer therapy. In: Driever PH, Rabkin SD (eds): Replication-Competent Viruses for Cancer Therapy. Monographs in Virology, Vol 22. Doerr HW, Karger, 2001, 160–182

  49. Reichard KW, Lorence RM, Cascino CJ: Selective replication of Newcastle disease virus (NDV) in cancer cells is associated with virus-induced cell fusion. Proc Am Assoc Cancer Res 33: 521, 1992

    Google Scholar 

  50. Pennisi E: Training viruses to attack cancers. Science 282: 1244–1246, 1998

    CAS  PubMed  Google Scholar 

  51. Nelson NJ: Scientific interest in Newcastle disease virus is reviving. Viruses and cancer. J Natl Cancer Inst 91: 1708–1710, 1999

    CAS  Google Scholar 

  52. Reichard KW, Lorence RM, Cascino CJ, Peeples ME, Walter RJ, Fernando MB, Reyes HM, Greager JA: Newcastle disease virus selectively kills human tumor cells. J Surg Res 52: 448–453, 1992

    Article  CAS  PubMed  Google Scholar 

  53. von Deimling A, von Ammon K, Schoenfeld D, Wiestler OD, Seizinger BR, Louis DN: Subsets of glioblastoma multiforme defined by molecular genetic analysis. Brain Pathol 3: 19–26, 1993

    CAS  PubMed  Google Scholar 

  54. Watanabe K, Tachinaba O, Sato K, Yonekawa Y, Kleihues P, Ohgaki H: Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol 6: 217–224, 1996

    CAS  PubMed  Google Scholar 

  55. Biernat W, Kleihues P, Yonekawa Y, Ohgaki H: Amplifi-cation and overexpression of MDM2 in primary (de novo) glioblastomas. J Neuropath Exp Neurol 56: 180–185, 1997

    CAS  PubMed  Google Scholar 

  56. Fazakerley J, Allsopp TE: Programmed cell death in virus infections of the nervous system. In: Gosztonyi G (ed) The Mechanisms of Neuronal Damage in Virus Infections of the Nervous System. CTMI 253: 95–119 (2001)

  57. Fueyo J, Alemany R, Gomez-Marzano C, Fuller GN, Khan A, Conrad CA, Liu TJ, Jiang H, Lemoine MG, Suzuki K, Sawaya R, Curiel DT, AlfredYung WK, Lang FF: Preclinical characterization of the antiglioma activity of a tropism-enhanced adenovirus targeted to the retinoblastoma pathway. J Ntl Cancer Inst 95: 652–660, 2003

    CAS  Google Scholar 

  58. Reichard KW, Lorence RM, Katubig BB, Peeples ME, Reyes HM: Retinoic acid enhances killing of neuroblastoma cells by Newcastle disease virus. J Pediatr Surg 28: 1221–1225, 1993

    CAS  PubMed  Google Scholar 

  59. Lorence RM, Katubig BB, Reichard KW, Reyes HM, Phuangsab A, Sassetti MD, Walter RJ, Peeples ME: Complete regression of human fibrosarcoma xenografts after local Newcastle disease virus therapy. Cancer Res 54: 6017–6021, 1994

    CAS  PubMed  Google Scholar 

  60. Lam KM: Apoptosis is chicken embryo fibroblasts caused by Newcastle disease virus. Vet Microbiol 47: 357–363, 1995

    Article  CAS  PubMed  Google Scholar 

  61. Lam KM, Vasconcelos AC, Bickford AA: Apoptosis as a cause of death in chicken embryos inoculated with Newcastle disease virus. Microb Pathol 19: 169–174, 1995

    CAS  Google Scholar 

  62. Reichard KW, Lorence RM, Cascino CJ: Selective replication of Newcastle disease virus (NDV) in cancer cells is associated with virus-induced cell fusion. Proc Am Assoc Cancer Res 33: 521, 1992

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Csatary, L., Gosztonyi, G., Szeberenyi, J. et al. MTH-68/H Oncolytic Viral Treatment in Human High-Grade Gliomas. J Neurooncol 67, 83–93 (2004). https://doi.org/10.1023/B:NEON.0000021735.85511.05

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:NEON.0000021735.85511.05

Navigation