Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Oncolytic activities of approved mumps and measles vaccines for therapy of ovarian cancer

Cancer Gene Therapy volume 12, pages 593–599 (2005)Cite this article

Abstract

Oncolytic viruses are promising cytoreductive agents for cancer treatment but extensive human testing will be required before they are made commercially available. Here, we investigated the oncolytic potential of two commercially available live attenuated vaccines, Moraten measles and Jeryl-Lynn mumps, in a murine model of intraperitoneal human ovarian cancer and compared their efficacies against a recombinant oncolytic measles virus (MV-CEA) that is being tested in a phase I clinical trial. The common feature of these viruses is that they express hemagglutinin and fusion therapeutic proteins that can induce extensive fusion of the infected cell with its neighbors, resulting in death of the cell monolayer. In vitro, the three viruses caused intercellular fusion in human ovarian cancer cells but with marked differences in fusion kinetics. MV-CEA was the fastest followed by Jeryl-Lynn mumps virus while Moraten measles virus was the slowest, although all viruses eventually caused comparable cell death 6 days postinfection. Tumor-bearing mice treated with 106 or 107 pfu (one thousand times the vaccine dose) of each of the three viruses responded favorably to therapy with significant prolongations in survival. All three viruses demonstrated equivalent antitumor potency. Commercially available Moraten measles and Jeryl-Lynn mumps vaccines warrant further investigation as potential anticancer agents.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Jemal A, Tiwari RC, Murray T, et al. American Cancer Society. Cancer statistics, 2004. CA Cancer J Clin. 2004;54:8–29.

    Article  PubMed  Google Scholar 

  2. NIH consensus conference. Ovarian cancer. Screening, treatment and follow-up. NIH Consensus Development Panel on Ovarian Cancer. JAMA. 1995;273:493–497.

  3. Stuart GC . First-line treatment regimens and the role of consolidation therapy in advanced ovarian cancer. Gynecol Oncol. 2003;90:S8–S15.

    Article  CAS  PubMed  Google Scholar 

  4. Russell SJ . Replicating vectors for cancer therapy: a question of strategy. Semin Cancer Biol. 1994;5:437–443.

    CAS  PubMed  Google Scholar 

  5. Kirn D, Martuza RL, Zwiebel J . Replication-selective virotherapy for cancer: biological principles, risk management and future directions. Nat Med. 2001;7:781–787.

    Article  CAS  PubMed  Google Scholar 

  6. Bell JC, Garson KA, Lichty BD, et al. Oncolytic viruses: programmable tumour hunters. Curr Gene Ther. 2002;2:243–254.

    Article  CAS  PubMed  Google Scholar 

  7. Everts B, Poel HG . Replication-selective oncolytic viruses in the treatment of cancer. Cancer Gene Ther. 2004 [Epub ahead of print].

  8. Peng KW, TenEyck CJ, Galanis E, et al. Intraperitoneal therapy of ovarian cancer using an engineered measles virus. Cancer Res. 2002;62:4656–4662.

    CAS  PubMed  Google Scholar 

  9. Peng KW, Facteau S, Wegman T, O'Kane D, Russell SJ . Non-invasive in vivo monitoring of trackable viruses expressing soluble marker peptides. Nat Med. 2002;8:527–531.

    Article  CAS  PubMed  Google Scholar 

  10. Griffin D . Measles Virus. In: Fielding B, Knipe D, Howley P, eds. Fields Virology. 4th ed. Philadelphia: Lippincott-Raven Publishers; 2001: 1401–1441.

    Google Scholar 

  11. Galanis E, Bateman A, Johnson K, et al. Use of viral fusogenic membrane glycoproteins as novel therapeutic transgenes in gliomas. Hum Gene Ther. 2001;12:811–821.

    Article  CAS  PubMed  Google Scholar 

  12. Esolen LM, Park SW, Hardwick JM, Griffin DE . Apoptosis as a cause of death in measles virus-infected cells. J Virol. 1995;69:3955–3958.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Nakamura T, Peng KW, Vongpunsawad S, et al. Antibody-targeted cell fusion. Nat Biotechnol. 2004;22:331–336.

    Article  CAS  PubMed  Google Scholar 

  14. Radecke F, Spielhofer P, Schneider H, et al. Rescue of measles viruses from cloned DNA. EMBO J. 1995;14:5773–5784.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rota JS, Wang ZD, Rota PA, et al. Comparison of sequences of the H, F, and N coding genes of measles virus vaccine strains. Virus Res. 1994;31:317–330.

    Article  CAS  PubMed  Google Scholar 

  16. Parks CL, Lerch RA, Walpita P, Wang HP, Sidhu MS, Udem SA . Comparison of predicted amino acid sequences of measles virus strains in the Edmonston vaccine lineage. J Virol. 2001;75:910–920.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Tatsuo H, Ono N, Tanaka K, Yanagi Y . SLAM (CDw150) is a cellular receptor for measles virus. Nature. 2000;406:893–897.

    Article  CAS  PubMed  Google Scholar 

  18. Dorig RE, Marcil A, Chopra A, Richardson CD . The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell. 1993;75:295–305.

    Article  CAS  PubMed  Google Scholar 

  19. Naniche D, Varior-Krishnan G, Cervoni F, et al. Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus. J Virol. 1993;67:6025–6032.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Bjorge L, Hakulinen J, Wahlstrom T, Matre R, Meri S . Complement-regulatory proteins in ovarian malignancies. Int J Cancer. 1997;70:14–25.

    Article  CAS  PubMed  Google Scholar 

  21. Lamb RA, Kolakofsky D . Paramyxoviridae: the viruses and their replication. In: Fielding B, Knipe D, Howley P, eds. Fields Virology. 4th edn. Philadelphia: Lippincott-Raven Publishers; 2001: 1305–1340.

    Google Scholar 

  22. Carbone KM, Wolinsky JS . Mumps Virus. In: Fielding B, Knipe D, Howley P, eds. Fields Virology. 4th edn. Philadelphia: Lippincott-Raven Publishers; 2001: 1381–1400.

    Google Scholar 

  23. Conover CA, Hartmann LC, Bradley S, et al. Biological characterization of human epithelial ovarian carcinoma cells in primary culture: the insulin-like growth factor system. Exp Cell Res. 1998;238:439–449.

    Article  CAS  PubMed  Google Scholar 

  24. Cathomen T, Naim HY, Cattaneo R . Measles viruses with altered envelope protein cytoplasmic tails gain cell fusion competence. J Virol. 1998;72:1224–1234.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Phuong LK, Allen C, Peng KW, et al. Use of a vaccine strain of measles virus genetically engineered to produce carcinoembryonic antigen as a novel therapeutic agent against glioblastoma multiforme. Cancer Res. 2003;63:2462–2469.

    CAS  PubMed  Google Scholar 

  26. 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.

    Article  CAS  PubMed  Google Scholar 

  27. Lin YL, Mettling C, Portales P, et al. Cell surface CCR5 density determines the postentry efficiency of R5 HIV-1 infection. Proc Natl Acad Sci USA. 2002;99:15590–15595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kozak SL, Platt EJ, Madani N, et al. CD4, CXCR-4, and CCR-5 dependencies for infections by primary patient and laboratory-adapted isolates of human immunodeficiency virus type 1. J Virol. 1997;71:873–882.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Li Y, Pong RC, Bergelson JM, et al. Loss of adenoviral receptor expression in human bladder cancer cells: a potential impact on the efficacy of gene therapy. Cancer Res. 1999;59:325–330.

    CAS  PubMed  Google Scholar 

  30. Cripe TP, Dunphy EJ, Holub AD, et al. Fiber knob modifications overcome low, heterogeneous expression of the coxsackievirus-adenovirus receptor that limits adenovirus gene transfer and oncolysis for human rhabdomyosarcoma cells. Cancer Res. 2001;61:2953–2960.

    CAS  PubMed  Google Scholar 

  31. Kanerva A, Wang M, Bauerschmitz GJ, et al. Gene transfer to ovarian cancer versus normal tissues with fiber-modified adenoviruses. Mol Ther. 2002;5:695–704.

    Article  CAS  PubMed  Google Scholar 

  32. Wickham TJ . Targeting adenovirus. Gene Ther. 2000;7:110–114.

    Article  CAS  PubMed  Google Scholar 

  33. Sillanaukee P, Ponnio M, Jaaskelainen IP . Occurrence of sialic acids in healthy humans and different disorders. Eur J Clin Invest. 1999;29:413–425.

    Article  CAS  PubMed  Google Scholar 

  34. Donin N, Jurianz K, Ziporen L, et al. Complement resistance of human carcinoma cells depends on membrane regulatory proteins, protein kinases and sialic acid. Clin Exp Immunol. 2003;131:254–263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Liszewski MK, Post TW, Atkinson JP . Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Annu Rev Immunol. 1991;9:431–455.

    Article  CAS  PubMed  Google Scholar 

  36. Gorter A, Meri S . Immune evasion of tumor cells using membrane-bound complement regulatory proteins. Immunol Today. 1999;20:576–582.

    Article  CAS  PubMed  Google Scholar 

  37. Fishelson Z, Donin N, Zell S, et al. Obstacles to cancer immunotherapy: expression of membrane complement regulatory proteins (mCRPs) in tumors. Mol Immunol. 2003;40 (2–4):109–123.

    Article  CAS  PubMed  Google Scholar 

  38. Russell SJ . RNA viruses as virotherapy agents. Cancer Gene Ther. 2002;9:961–966.

    Article  CAS  PubMed  Google Scholar 

  39. Yoon TK, Shichinohe T, Laquerre S, et al. Selectively replicating adenoviruses for oncolytic therapy. Curr Cancer Drug Targets. 2001;1:85–107.

    Article  CAS  PubMed  Google Scholar 

  40. Cornelis JJ, Salome N, Dinsart C, Rommelaere J . Vectors based on autonomous parvoviruses: novel tools to treat cancer? J Gene Med. 2004;6 (Suppl 1):S193–S202.

    Article  CAS  PubMed  Google Scholar 

  41. Giedlin MA, Cook DN, Dubensky Jr TW . Vesicular stomatitis virus: an exciting new therapeutic oncolytic virus candidate for cancer or just another chapter from Field's Virology? Cancer Cell. 2003;4:241–243.

    Article  CAS  PubMed  Google Scholar 

  42. Fulci G, Chiocca EA . Oncolytic viruses for the therapy of brain tumors and other solid malignancies: a review. Front Biosci. 2003;8:e346–e360.

    Article  CAS  PubMed  Google Scholar 

  43. Cranshaw ML, Leak LV . Milky spots of the omentum: a source of peritoneal cells in the normal and stimulated animal. Arch Histol Cytol. 1990;53 (Suppl):165–177.

    Article  PubMed  Google Scholar 

  44. Wijffels JF, Hendrickx RJ, Steenbergen JJ, et al. Milky spots in the mouse omentum may play an important role in the origin of peritoneal macrophages. Res Immunol. 1992;143:401–409.

    Article  CAS  PubMed  Google Scholar 

  45. Hagiwara A, Takahashi T, Sawai K, et al. Milky spots as the implantation site for malignant cells in peritoneal dissemination in mice. Cancer Res. 1993;53:687–692.

    CAS  PubMed  Google Scholar 

  46. Lopes CAM, Gupta A, Koppe MJ, et al. Metastatic pattern of CC531 colon carcinoma cells in the abdominal cavity: an experimental model of peritoneal carcinomatosis in rats. Eur J Surg Oncol. 2001;27:359–363.

    Article  Google Scholar 

  47. Asada T . Treatment of human cancer with mumps virus. Cancer. 1974;34:1907–1928.

    Article  CAS  PubMed  Google Scholar 

  48. Okuno Y, Asada T, Yamanishi K, et al. Studies on the use of mumps virus for treatment of human cancer. Biken J. 1978;21:37–49.

    CAS  PubMed  Google Scholar 

  49. Shimizu Y, Hasumi K, Okudaira Y, et al. Immunotherapy of advanced gynecologic cancer patients utilizing mumps virus. Cancer Detect Prev. 1988;12:487–495.

    CAS  PubMed  Google Scholar 

  50. Rubin SA, Pletnikov M, Taffs R, et al. Evaluation of a neonatal rat model for prediction of mumps virus neurovirulence in humans. J Virol. 2000;74:5382–5384.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Saika S, Kidokoro M, Aoki A, et al. Neurovirulence of mumps virus: intraspinal inoculation test in marmosets. Biologicals. 2004;32:147–152.

    Article  CAS  PubMed  Google Scholar 

  52. Dingli D, Peng KW, Harvey ME, et al. Image-guided radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal sodium iodide symporter. Blood. 2004;103:1641–1646.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was funded by Grants from the NIH HL66958-04P4 and CA100634-01, Mayo Foundation, Harold W Siebens Foundation and George W Eisenberg Foundation.

Author information

Authors and Affiliations

  1. Toxicology Core, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

    Rae Myers, Suzanne Greiner, Mary Harvey, Diane Soeffker, Stephen J Russell & Kah-Whye Peng

  2. Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

    Marie Frenzke, Mark J Federspiel, Stephen J Russell & Kah-Whye Peng

  3. Merck Research Laboratories, West Point, Pennsylvania, USA

    Katalin Abraham & Alan Shaw

  4. Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, Israel

    Shmuel Rozenblatt

  5. Viral Vector Production Laboratory, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

    Mark J Federspiel

  6. Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

    Kah-Whye Peng

Authors
  1. Rae Myers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Suzanne Greiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mary Harvey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Diane Soeffker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marie Frenzke
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Katalin Abraham
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alan Shaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shmuel Rozenblatt
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mark J Federspiel
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Stephen J Russell
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kah-Whye Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kah-Whye Peng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Myers, R., Greiner, S., Harvey, M. et al. Oncolytic activities of approved mumps and measles vaccines for therapy of ovarian cancer. Cancer Gene Ther 12, 593–599 (2005). https://doi.org/10.1038/sj.cgt.7700823

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.cgt.7700823

Keywords

This article is cited by

Search

Advanced search

Quick links