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TumorDiagnostik & Therapie 2012; 33(5): 279-283
DOI: 10.1055/s-0032-1313090
Thieme Onkologie aktuell
© Georg Thieme Verlag KG Stuttgart · New York

Oncolytic Viruses to Treat Ovarian Cancer Patients – a Review of Results From Clinical Trials

Onkolytische Viren zur Behandlung von Ovarialkarzinompatientinnen – Eine Übersicht der Ergebnisse klinischer Studien
A. D. Hartkopf
1   Department of Obstetrics and Gynecology, University of Tübingen, Tübingen
,
T. Fehm
1   Department of Obstetrics and Gynecology, University of Tübingen, Tübingen
,
M. Wallwiener
2   Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg
,
U. Lauer
3   Department of Gastroenterology and Hepatology, University of Tübingen, Tübingen
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
23. August 2012 (online)

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Zusammenfassung

Onkolytische Viren sind replikationsfähige „lebende“ Viren. Sie infizieren hochselektiv Tumorzellen, vermehren sich in diesen und zerstören sie dabei. Aufgrund der enormen Fortschritte auf dem Gebiet der Gen- und Biotechnologie kommt die Virotherapie zunehmend in klinischen Studien zum Einsatz und erweist sich als äußerst sicher, nebenwirkungsarm und effektiv. Insbesondere findet sich bei der Behandlung von Ovarialkarzinompatientinnen ein wichtiger Forschungsschwerpunkt. Zum einen liegt dies an der schlechten Prognose der Erkrankung und der hieraus resultierenden Notwendigkeit neuer Therapiemodalitäten. Zum anderen breitet sich das Ovarialkarzinom typischerweise lokoregionär aus, woraus sich die spezielle Möglichkeit der intraperitonealen Applikation onkolytischer Viren ergibt. Die vorliegende Arbeit fasst die vielversprechenden Ergebnisse klinischer Studien zur Behandlung von Ovarialkarzinompatientinnen mit onkolytischen Viren zuammen.

Abstract

Oncolytic viruses are replication competent “live” viruses. They infect tumor cells, replicate highly selective inside and thereby destroy them. Because of the enormous advances in the field of genetic engineering and biotechnology during the last decade, virotherapy is increasingly used within clinical trials and proved to be safe and effective. In particular, treatment of ovarian cancer patients is one main focus of research. On the one hand, this is due to the poor prognosis of this dismal entity, resulting in the urgent need for novel therapeutics. On the other hand, as ovarian cancer typically spreads within the peritoneal cavity, intraperitoneal administration of oncolytic viruses is feasible. This paper provides an overview of promising results from clinical trials to treat ovarian cancer patients with oncolytic viruses.

Key words

ovarian cancer - breast - biomarker - cell culture

Schlüsselwörter

Biomarker - Mammakarzinom - Ovarmalignom - Zellkultur
 

  • References

  • 1 Husmann G. Robert Koch-Inst Hrsg. Krebs in Deutschland: 2005/2006; Häufigkeiten und Trends; Eine gemeinsame Veröffentlichung des Robert Koch-Instituts und der Gesellschaft der Epidemiologischen Krebsregister in Deutschland e.V. Berlin: Robert Koch-Institut; 2010
    Google Scholar
  • 2 NIH consensus conference. Ovarian cancer. Screening, treatment, and follow-up. NIH Consensus Development Panel on Ovarian Cancer. JAMA 1995; 273: 491-497
    CrossrefPubMedGoogle Scholar
  • 3 Heitz F, Harter P, Zelazny J et al. Antiangiogenic approaches in ovarian cancer therapy. Geburtsh Frauenheilk 2010; 70: 791-797
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 4 Hartkopf AD, Fehm T, Wallwiener D et al. Oncolytic virotherapy of gynecologic malignancies. Gynecol Oncol 2011; 120: 302-310
    CrossrefPubMedGoogle Scholar
  • 5 Bitzer M, Lauer UM. [Oncolytic viruses for genetic therapy of gastrointestinal tumors]. Z Gastroenterol 2003; 41: 667-674
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 6 Kelly E, Russell SJ. History of oncolytic viruses: genesis to genetic engineering. Mol Ther 2007; 15: 651-659
    PubMedGoogle Scholar
  • 7 Bluming AZ, Ziegler JL. Regression of Burkittʼs lymphoma in association with measles infection. Lancet 1971; 2: 105-106
    PubMedGoogle Scholar
  • 8 Zygiert Z. Hodgkinʼs disease: remissions after measles. Lancet 1971; 1: 593
    PubMedGoogle Scholar
  • 9 Huebner RJ, Rowe WP, Schatten WE et al. Studies on the use of viruses in the treatment of carcinoma of the cervix. Cancer 1956; 9: 1211-1218
    CrossrefPubMedGoogle Scholar
  • 10 Cassel WA, Garrett RE. Newcastle disease virus as an antineoplastic agent. Cancer 1965; 18: 863-868
    CrossrefPubMedGoogle Scholar
  • 11 Liu TC, Galanis E, Kirn D. Clinical trial results with oncolytic virotherapy: a century of promise, a decade of progress. Nat Clin Pract Oncol 2007; 4: 101-117
    CrossrefPubMedGoogle Scholar
  • 12 Kirn D, Martuza RL, Zwiebel J. Replication-selective virotherapy for cancer: Biological principles, risk management and future directions. Nat Med 2001; 7: 781-787
    CrossrefPubMedGoogle Scholar
  • 13 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 1988; 80: 1305-1312
    CrossrefPubMedGoogle Scholar
  • 14 Peplinski GR, Tsung AK, Casey MJ et al. In vivo murine tumor gene delivery and expression by systemic recombinant vaccinia virus encoding interleukin-1beta. Cancer J Sci Am 1996; 2: 21-27
    PubMedGoogle Scholar
  • 15 Stojdl DF, Lichty B, Knowles S et al. Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nat Med 2000; 6: 821-825
    CrossrefPubMedGoogle Scholar
  • 16 Geletneky K, Hartkopf AD, Krempien R et al. Improved killing of human high-grade glioma cells by combining ionizing radiation with oncolytic parvovirus H-1 infection. J Biomed Biotechnol 2010; 2010: 350748
    PubMedGoogle Scholar
  • 17 Zimmermann M, Armeanu S, Smirnow I et al. Human precision-cut liver tumor slices as a tumor patient-individual predictive test system for oncolytic measles vaccine viruses. Int J Oncol 2009; 34: 1247-1256
    PubMedGoogle Scholar
  • 18 Coffey MC, Strong JE, Forsyth PA et al. Reovirus therapy of tumors with activated Ras pathway. Science 1998; 282: 1332-1334
    CrossrefPubMedGoogle Scholar
  • 19 Bauerschmitz G, Breidenbach M, Dall P et al. Mehrfach modifizierte onkolytische Adenoviren in der präklinischen Testung an Ovarialkarzinomzellen. Geburtsh Frauenheilk 2007; 67: 1102-1108
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 20 Cutts FT, Markowitz LE. Successes and failures in measles control. J Infect Dis 1994; 170 (Suppl. 01) S32-S41
    CrossrefPubMedGoogle Scholar
  • 21 Dorig RE, Marcil A, Chopra A et al. The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell 1993; 75: 295-305
    CrossrefPubMedGoogle Scholar
  • 22 Anderson BD, Nakamura T, Russell SJ et al. High CD46 receptor density determines preferential killing of tumor cells by oncolytic measles virus. Cancer Res 2004; 64: 4919-4926
    CrossrefPubMedGoogle Scholar
  • 23 Peng KW, Facteau S, Wegman T et al. Non-invasive in vivo monitoring of trackable viruses expressing soluble marker peptides. Nat Med 2002; 8: 527-531
    CrossrefPubMedGoogle Scholar
  • 24 Galanis E, Hartmann LC, Cliby WA et al. Phase I trial of intraperitoneal administration of an oncolytic measles virus strain engineered to express carcinoembryonic antigen for recurrent ovarian cancer. Cancer Res 2010; 70: 875-882
    CrossrefPubMedGoogle Scholar
  • 25 Milton GW, Brown MM. The limited role of attenuated smallpox virus in the management of advanced malignant melanoma. Aust N Z J Surg 1966; 35: 286-290
    CrossrefPubMedGoogle Scholar
  • 26 Hunter-Craig I, Newton KA, Westbury G et al. Use of vaccinia virus in the treatment of metastatic malignant melanoma. Br Med J 1970; 2: 512-515
    CrossrefPubMedGoogle Scholar
  • 27 Arakawa Jr. S, Hamami G, Umezu K et al. Clinical trial of attenuated vaccinia virus AS strain in the treatment of advanced adenocarcinoma. Report on two cases. J Cancer Res Clin Oncol 1987; 113: 95-98
    CrossrefPubMedGoogle Scholar
  • 28 Gomella LG, Mastrangelo MJ, McCue PA et al. Phase i study of intravesical vaccinia virus as a vector for gene therapy of bladder cancer. J Urol 2001; 166: 1291-1295
    CrossrefPubMedGoogle Scholar
  • 29 McCart JA, Ward JM, Lee J et al. Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes. Cancer Res 2001; 61: 8751-8757
    PubMedGoogle Scholar
  • 30 Hung CF, Tsai YC, He L et al. Vaccinia virus preferentially infects and controls human and murine ovarian tumors in mice. Gene Ther 2007; 14: 20-29
    CrossrefPubMedGoogle Scholar
  • 31 Chalikonda S, Kivlen MH, OʼMalley ME et al. Oncolytic virotherapy for ovarian carcinomatosis using a replication-selective vaccinia virus armed with a yeast cytosine deaminase gene. Cancer Gene Ther 2008; 15: 115-125
    CrossrefPubMedGoogle Scholar
  • 32 Hirasawa K, Nishikawa SG, Norman KL et al. Oncolytic reovirus against ovarian and colon cancer. Cancer Res 2002; 62: 1696-1701
    PubMedGoogle Scholar
  • 33 Lal R, Harris D, Postel-Vinay S et al. Reovirus: Rationale and clinical trial update. Curr Opin Mol Ther 2009; 11: 532-539
    PubMedGoogle Scholar
  • 34 Cohn DE, Nuovo G, Coffey MC et al. Phase I/II trial of reovirus serotype 3-Dearing strain in patients with recurrent ovarian cancer. J Clin Oncol 2010; 28: 15s (Abstr. TP253)
    PubMedGoogle Scholar
  • 35 Phelps MA, Cohn DE, OʼMalley DM et al. Reovirus replication in ovarian and peritoneal tumors after intravenous administration. Proceedings of the 101st Annual Meeting of the American Association for Cancer Research 2010; Abstract No. 2594
    PubMedGoogle Scholar
  • 36 Vollmer CM, Ribas A, Butterfield LH et al. p 53 selective and nonselective replication of an E1B-deleted adenovirus in hepatocellular carcinoma. Cancer Res 1999; 59: 4369-4374
    PubMedGoogle Scholar
  • 37 Bischoff JR, Kirn DH, Williams A et al. An adenovirus mutant that replicates selectively in p 53-deficient human tumor cells. Science 1996; 274: 373-376
    CrossrefPubMedGoogle Scholar
  • 38 Yuan ZY, Zhang L, Li S et al. [Safety of an E1B deleted adenovirus administered intratumorally to patients with cancer]. Ai Zheng 2003; 22: 310-313
    PubMedGoogle Scholar
  • 39 Vasey PA, Shulman LN, Campos S et al. Phase I trial of intraperitoneal injection of the E1B-55-kd-gene-deleted adenovirus ONYX-015 (dl1520) given on days 1 through 5 every 3 weeks in patients with recurrent/refractory epithelial ovarian cancer. J Clin Oncol 2002; 20: 1562-1569
    CrossrefPubMedGoogle Scholar
  • 40 Liu HL, Chen J. Oncolytic virus as an agent for the treatment of malignant ascites. Cancer Biother Radiopharm 2009; 24: 99-102
    CrossrefPubMedGoogle Scholar
  • 41 Bauerschmitz GJ, Lam JT, Kanerva A et al. Treatment of ovarian cancer with a tropism modified oncolytic adenovirus. Cancer Res 2002; 62: 1266-1270
    PubMedGoogle Scholar
  • 42 Kimball KJ, Preuss MA, Barnes MN et al. A phase I study of a tropism-modified conditionally replicative adenovirus for recurrent malignant gynecologic diseases. Clin Cancer Res 2010; 16: 5277-5287
    CrossrefPubMedGoogle Scholar
  • 43 Fisher K. Striking out at disseminated metastases: the systemic delivery of oncolytic viruses. Curr Opin Mol Ther 2006; 8: 301-313
    PubMedGoogle Scholar
  • 44 Hemminki A, Belousova N, Zinn KR et al. An adenovirus with enhanced infectivity mediates molecular chemotherapy of ovarian cancer cells and allows imaging of gene expression. Mol Ther 2001; 4: 223-231
    CrossrefPubMedGoogle Scholar
  • 45 Lolkema MP, Arkenau HT, Harrington K et al. A phase I study of the combination of intravenous reovirus type 3 Dearing and gemcitabine in patients with advanced cancer. Clin Cancer Res 2011; 17: 581-588
    CrossrefPubMedGoogle Scholar
  • 46 Fulci G, Breymann L, Gianni D et al. Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses. Proc Natl Acad Sci USA 2006; 103: 12873-12878
    CrossrefPubMedGoogle Scholar
  • 47 Mader EK, Maeyama Y, Lin Y et al. Mesenchymal stem cell carriers protect oncolytic measles viruses from antibody neutralization in an orthotopic ovarian cancer therapy model. Clin Cancer Res 2009; 15: 7246-7255
    CrossrefPubMedGoogle Scholar
  • 48 Willmon C, Harrington K, Kottke T et al. Cell carriers for oncolytic viruses: Fed Ex for cancer therapy. Mol Ther 2009; 17: 1667-1676
    CrossrefPubMedGoogle Scholar
  • 49 Cerullo V, Pesonen S, Diaconu I et al. Oncolytic adenovirus coding for granulocyte macrophage colony-stimulating factor induces antitumoral immunity in cancer patients. Cancer Res 2010; 70: 4297-4309
    CrossrefPubMedGoogle Scholar
  • 50 Koski A, Kangasniemi L, Escutenaire S et al. Treatment of cancer patients with a serotype 5/3 chimeric oncolytic adenovirus expressing GMCSF. Mol Ther 2010; 18: 1874-1884
    CrossrefPubMedGoogle Scholar
  • 51 du Bois A, Schmalfeldt B, Meier W et al. Onkologie. Ovarialkarzinom – Ist die intraperitoneale Therapie wirklich neuer Standard?. Geburtsh Frauenheilk 2006; 66: 604-605
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 52 Lage H. Mechanismen der Chemotherapieresistenz beim Ovarialkarzinom. Geburtsh Frauenheilk 2007; 67: 831-836
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 53 Hartkopf AD, Fehm T, Wallwiener D et al. Oncolytic virotherapy of breast cancer. Gynecol Oncol 2011; 123: 164-171
    CrossrefPubMedGoogle Scholar