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Deutsche Zeitschrift für Onkologie 2007; 39(4): 148-152
DOI: 10.1055/s-2007-986019
Forschung

© Karl F. Haug Verlag in MVS Medizinverlage Stuttgart GmbH & Co. KG

Tumortherapie mit onkolytischen Viren bei malignen Hirntumoren

Thomas Neßelhut1 , Dagmar Marx1 , J. J. Neßelhut1 , N. Cillien1 , Wilfried Stücker2 , Ingo Wilke3 , Wolfgang Lüke4
  • 1Institut für Tumortherapie, Duderstadt
  • 2IOZK, Köln
  • 3FZMB, Bad Langensalza
  • 4IOZK, Köln (derzeitige Adresse Deutsches Primatenzentrum Göttingen)
Further Information

Publication History

Publication Date:
20 December 2007 (online)

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Zusammenfassung

Die schulmedizinischen Behandlungsmethoden für maligne Hirntumoren sind nach wie vor unbefriedigend. Dies gilt insbesondere für die aggressivste Form, das Glioblastoma multiforme WHO IV. Deshalb ist die Entwicklung neuer, innovativer Strategien, wie z.B. die spezifische Immuntherapie, für die Therapie von malignen Hirntumoren von eminent wichtiger Bedeutung. Als eine der wichtigsten und effektivsten Säulen der spezifischen Immuntherapie von malignen Hirntumoren hat sich die Behandlung mit aus Monozyten abgeleiteten autologen dendritischen Zellen herauskristallisiert. In mehreren klinischen Studien konnte gezeigt werden, dass die Behandlung von Hirntumoren mit dendritischen Zellen allein oder in Kombination mit anderen Therapien erfolgreich sein kann. Einen weiteren Erfolg versprechenden Weg stellt die Behandlung mit onkolytischen Viren dar.

Summary

Malignant brain tumors belong to the tumors with up to now unfavorable prognosis. The most aggressive form, glioblastoma multiforme (GBM WHO IV), is categorized as incurable with average survivals less than 18 months, in spite of standard treatment (surgery, radiation therapy and chemotherapy).

Although the tumor is hidden behind the blood brain barrier, immune effector cells can be recruited into the central nervous system. This makes an active specific immunotherapy feasible. Meanwhile, several groups have shown that a specific immunotherapy with monocyte-derived dendritic cells (MoDC) can induce a clinical antitumor response in patients with malignant brain tumors. Treatment failure to DC therapy can be due to loss of antigen expression restricted on MHC-class I and II molecules leading to a lower immunogenity of the tumors. Beside dendritic cell therapy another promising approach is the treatment with replication-selective viruses, also called oncolytic viruses such as Newcastle Disease Virus (NDV). Cancer cells infected with NDV can be killed directly by the virus or the infection can lead to the induction of an immune response against the cancer cell.

Schlüsselwörter

Karzinom - dendritische Zelle - Immuntherapie - NDV - onkolytische Viren

Keywords

Cancer - dendritic cell - immune therapy - NDV - oncolytic viruses

Literatur

  • 01 Alexander D J. Newcastle disease virus - An avian paramyxovirus. In: Alexander DJ (ed): New Castle Disease. Boston; Kluwer Academic 1988: 11-22
    Google Scholar
  • 02 Bai L, Koopmann J, Fiola C, Fournier P, Schirrmacher V. Dendritic cells pulsed with viral oncolysates potently stimulate autologous T cells from cancer patients.  Int J Oncol. 2002;  21 685-694
    Google Scholar
  • 03 Cassel W A, Garrett R E. Newcastle disease virus as an antineoplastic agent.  Cancer. 1965;  18 863-868
    Google Scholar
  • 04 Csatary L K, Bakacs T. Newcastle disease virus vaccine (MTH-68/H) in a patient with high-grade glioblatoma.  JAMA. 1999;  281 (17) 1588-1589
    Google Scholar
  • 05 Csatary L K, Gosztonyi G, Szeberenyi J, Fabian Z, Liszka V, Bodey B, Csatar C M. MTH-68/H oncolytic viral treatment in human high-grade gliomas.  J Neurooncol. 2004;  67 (1-2) 83-93
    Google Scholar
  • 06 Pace N G de. Sulla scomparsa di un enorme cancro vegetante del callo dell`utero senza cura chrurgica.  Ginecologia. 1912;  9 82-88
    Google Scholar
  • 07 Freeman A I, Zackay-Rones Z, Gomori J M, Linetsky E, Rasooly L, Greenbaum E, Rozenman-Yair S, Panet A, Libson E, Irving C S, Galun E, Siegal T. Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme.  Molecular Therapy. 2005;  13 221-228
    Google Scholar
  • 08 Geoerger B, Grill J, Opolon P, Morizet J, Aubert G, Terrier-Lacombe M J, Bressac De-Paillerets B, Barrois M, Feunteum J, Kirn d H, Vassal G. Oncolytic activity oft he E1B-55-kDa-deleted adenovirus ONYX-015 is independent of cellular p53 status in human malignant glioma xenografts.  Cancer Res. 2002;  62 (3) 764-772
    Google Scholar
  • 09 Geoerger B, Vassal G, Opolon P, Dirven C M, Morizet J, Laudani L, Grill J, Giaccone G, Vandertop W P, Gerritsen W R, Beusechem V W van. Oncolytic activity of p53-expressing conditionally replicative adenovirus AdDelta24-p53 against human malignant glioma.  Cancer Res. 2004;  64 (16) 5753-9
    Google Scholar
  • 10 Lorence R M, Roberts M S, Groene W S, Rabin H. Replication-competent, oncolytic Newcastle disease virus for cancer therapy. In: Hernaiz-Driever, Rabkin (eds): Replication competent viruses for cancer therapy. Monographs Virology (Vol. 22). Basel; Karger 2001: 160-182
    Google Scholar
  • 11 Lorence R M, Pecora, Major, Hotte, Laurie, Roberts, Groene, Bamat. Overview of phase I studies of intravenous administration of PV107, an oncolytic virus.  Current Opinion in Molecular Therapeutics.. 2003;  5 618-624
    PubMedGoogle Scholar
  • 12 Markert J M, Medlock M D, Rabkin S D, Gillespie G Y, Todo T, Hunter W D, Palmer C A, Feigenbaum F, Tornatore C, Tufaro F, Martuza R L. Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial.  Gene Ther. 2000;  7 (10) 867-74
    CrossrefPubMedGoogle Scholar
  • 13 Nemunaitis J. Oncolytic viruses yesterday and today.  J Oncol Manag. 1999;  8 (5) 14-24
    PubMedGoogle Scholar
  • 14 Neßelhut J, Neßelhut T, Chang R, Marx D, Brockmann W, Wilke I, Matthes C, Lorenzen D, Stücker w, Peters J H, Lüke W. Dendritic cell therapy in glioblastoma multiforme.  J Clin Oncol. 2007;  25 (18S) 2065
    PubMedGoogle Scholar
  • 15 Papanastassiou V, Ramplin R, Fraser M, Petty R, Hadley D, Nicoll J, Harland J, Mabbs R, Brown M. The potential for efficacy of the modified (ICP 34.5 (-)) herpes simplex virus HSV1716 following intratumoural injection into human malignant glioma: a proof of principle study.  Gene Ther. 2002;  9 (6) 398-406
    CrossrefPubMedGoogle Scholar
  • 16 Rainov N G, Ren H. Oncolytic viruses for treatment of malignant brain tumors.  Acta Neurochir Suppl. 2003;  88 113-123
    PubMedGoogle Scholar
  • 17 Rampling R, Cruickhank G, Papanastassiou V, Nicoll J, Hadley D, Brennan D, Petty R, MacLean A, Harland J, McKie E, Mabbs R, Brown M. Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma.  Gene Ther.. 2000;  7 859-866
    CrossrefPubMedGoogle Scholar
  • 18 Reichard K W, Lorence R M, Cascino C J, Peeples M E, Walter R J, Fernando M B, Reyes H M, Greager J A. Newcastle disease virus selectively kills human tumor cells.  J Surg Res. 1992;  52 (5) 448-53
    CrossrefPubMedGoogle Scholar
  • 19 Ries S J, Brandts C H. Oncolytic viruses for the treatment of cancer: current strategies and clinical trials.  Drug Discov Today. 2004;  9 (17) 759-68
    CrossrefPubMedGoogle Scholar
  • 20 Rutkowski S, Vleeschouwer S de, Kaempgen E, Wolff J E, Kuhl J, Demaerel P, Warmuth-Metz M, Flamen P, Calenbergh F van, Plets C, Sorensen N, Opitz A, Gool S W van. Surgery and adjuvant dendritic cell-based tumour vaccination for patients with relapsed malignant glioma, a feasibility study.  Br J Cancer. 2004;  91 (9) 1656-62
    PubMedGoogle Scholar
  • 21 Samson A C R. Virus Structure. In: Alexander DJ (ed): Newcastle Disease. Boston; Kluwer Academics 1988: 23-44
    Google Scholar
  • 22 Schirrmacher V, Griesbach A, Ahlert T. Antitumor effects of Newcastle disease virus in vivo: Local versus systemic effects.  Int J Oncol. 2001;  18 (5) 94-952
    PubMedGoogle Scholar
  • 23 Schirrmacher V. 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. 2005;  54 (6) 587-98
    PubMedGoogle Scholar
  • 24 Schneider T, Gerhards R, Kirches E, Firsching R. Preliminary results of active specific immunization with modified tumor cell vaccine in glioblastoma multiforme.  J Neuooncol. 2001;  53 (1) 39-46
    PubMedGoogle Scholar
  • 25 Shah A C, Benos D, Gillepsie G Y, Markert J M. Oncolytic viruses: clinical applications as vectors for the treatment of malignant gliomas.  J Neurooncol. 2003;  65 (3) 2023-2026
    PubMedGoogle Scholar
  • 26 Stojdl D F, Lichty B, Knowles S. Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus.  Nat Med. 2000;  6 821-825
    CrossrefPubMedGoogle Scholar
  • 27 Vähä-Koskela M J, Heikkilä J E, Hinkkanen A E. Oncolytic viruses in cancer therapy.  Cancer Lett. 2007;  254 (2) 178-216
    CrossrefPubMedGoogle Scholar
  • 28 Wagner S, Csatary C M, Gosztonyi G, Koch H C, Hartmann C, Peters O, Hernaiz-Driever P, Theallier-Janko A, Zintl F, Längler A, Wolff J E, Csatary L K. Combined treatment of pediatric high-grade glioma with the oncolytic viral strain MTH-68/H and oral valproic acid.  APMIS. 2006;  114 (10) 731-743
    CrossrefPubMedGoogle Scholar
  • 29 Wollmann G, Tattersal P, van den Polan. Targeting human glioblastoma cells: comparison of nine viruses with oncolytic potential.  J Virol. 2005;  79 (10) 6005-6022
    CrossrefPubMedGoogle Scholar
  • 30 Yamanaka R, Abe T, Yajima N, Tsuchiya N, Homma J, Kobayashi T, Narita M, Takahashi M, Tanaka R. Vaccination of recurrent glioma patients with tumour lysate-pulsed dendritic cells elicits immune responses: results of a clinical phase I/II trial.  Br J Cancer. 2003;  89 (7) 1172-1179
    CrossrefPubMedGoogle Scholar

Korrespondenzadresse:

Dr. med. Thomas Neßelhut

Institut für Tumortherapie

Hinterstraße 53

37115 Duderstadt

Email: thomas.nesselhut@dr-nesselhut.de

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