Breast Cancer Research and Treatment

, Volume 99, Issue 2, pp 177–184 | Cite as

A measles virus vaccine strain derivative as a novel oncolytic agent against breast cancer

  • Cari J. McDonald
  • Charles Erlichman
  • James N. Ingle
  • Gabriela A. Rosales
  • Cory  Allen
  • Suzanne M. Greiner
  • Mary E. Harvey
  • Paula J. Zollman
  • Stephen J. Russell
  • Evanthia Galanis
Preclinical investigation

Summary

Breast cancer is the most common malignancy and the second leading cause of female cancer mortality in the United States. There is an urgent need for development of novel therapeutic approaches. In this study, we investigated the antitumor potential of a novel viral agent, an attenuated strain of measles virus deriving from the Edmonston vaccine lineage, genetically engineered to produce carcinoembryonic antigen (CEA) against breast cancer. CEA production as the virus replicates can serve as a marker of viral gene expression. Infection of a variety of breast cancer cell lines including MDA-MB-231, MCF7 and SkBr3 at different multiplicities of infection (MOIs) from 0.1 to 10 resulted in significant cytopathic effect consisting of extensive syncytia formation and massive cell death at 72–96 h from infection. All breast cancer lines overexpressed the measles virus receptor CD46 and supported robust viral replication, which correlated with CEA production. TUNEL assays indicated an apoptotic mechanism of syncytial death. The efficacy of this approach in vivo was examined in a subcutaneous Balb C/nude mouse model of MDA-MB-231 cells. Intravenous administration of MV-CEA at a total dose of 1.2×107 TCID50 resulted in statistically significant tumor growth delay ( p=0.005) and prolongation of survival ( p=0.001). In summary, MV-CEA has potent antitumor activity against breast cancer lines and xenografts. Monitoring marker peptide levels in the serum could serve as a low-risk method of detecting viral gene expression during treatment and could allow dose optimization and individualization of treatment. Trackable measles virus derivatives merit further exploration in breast cancer treatment.

Keywords

breast cancer CEA measles virus MV-CEA virotherapy 

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Notes

Acknowledgements

Supported by a Prospect Creek Foundation Grant. Also supported in part by an Eagles’ Grant (EG) and by Breast SPORE P50CA 116201-1 (JNI, EG).

References

  1. 1.
    Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ Cancer statistics CA Cancer J Clin 55(1): 10–30, 2005PubMedCrossRefGoogle Scholar
  2. 2.
    Wild TF, Malvoisin E, Buckland R Measles virus: both the haemagglutinin and fusion glycoproteins are required for fusionJ Gen Virol 1991, 72(Pt 2): 439–442PubMedCrossRefGoogle Scholar
  3. 3.
    Dorig RE, Marcil A, Chopra A, Richardson CD The human CD46 molecule is a receptor for measles virus (Edmonston strain)Cell 1993, 75(2): 295–305PubMedCrossRefGoogle Scholar
  4. 4.
    Naniche D, Varior-Krishnan G, Cervoni F, Wild TF, Rossi B, Rabourdin-Combe C, Gerlier D Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virusJ Virol 1993, 67(10): 6025–6032PubMedGoogle Scholar
  5. 5.
    Tatsuo H, Ono N, Tanaka K, Yanagi Y SLAM (CDw150) is a cellular receptor for measles virus Nature 2000, 406(6798): 893–897PubMedCrossRefGoogle Scholar
  6. 6.
    Jurianz K, Ziegler S, Garcia-Schuler H, Kraus S, Bohana-Kashtan O, Fishelson Z, Kirschfink M Complement resistance of tumor cells: basal and induced mechanismsMol Immunol 1999, 36(13–14): 929–939PubMedCrossRefGoogle Scholar
  7. 7.
    Madjd Z, Durrant LG, Pinder SE, Ellis IO, Ronan J, Lewis S, Rushmere NK, Spendlove I Do poor-prognosis breast tumours express membrane cofactor proteins (CD46)?Cancer Immunol Immunother 2005, 54(2): 149–156PubMedCrossRefGoogle Scholar
  8. 8.
    Peng KW, Ahmann GJ, Pham L, Greipp PR, Cattaneo R, Russell SJ Systemic therapy of myeloma xenografts by an attenuated measles virus Blood 2001, 98(7): 2002–2007PubMedCrossRefGoogle Scholar
  9. 9.
    Peng KW, TenEyck CJ, Galanis E, Kalli KR, Hartmann LC, Russell SJ Intraperitoneal therapy of ovarian cancer using an engineered measles virus Cancer Res 2002, 62(16): 4656–4662PubMedGoogle Scholar
  10. 10.
    Cutts FT, Markowitz LE Successes and failures in measles control J Infect Dis 1994, 170(Suppl 1): S32–S41PubMedGoogle Scholar
  11. 11.
    Yanagi Y [The cellular receptor for measles virus] Uirusu 2001, 51(2): 201–208PubMedGoogle Scholar
  12. 12.
    Schneider U, von Messling V, Devaux P, Cattaneo R Efficiency of measles virus entry and dissemination through different receptors J Virol 2002, 76(15): 7460–7467PubMedCrossRefGoogle Scholar
  13. 13.
    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(5): 527–531PubMedCrossRefGoogle Scholar
  14. 14.
    Dingli D, Peng KW, Harvey ME, Greipp PR, O’Connor MK, Cattaneo R, Morris JC, Russell SJ: Image-guided radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal sodium iodide symporter. Blood 103(5): 1641–1646, 2004. Epub 2003 Nov 1646. Write to the Help Desk NCBI | NLM | NIH Department of Health & Human Services Privacy Statement | Freedom of Information Act | DisclaimerGoogle Scholar
  15. 15.
    Radecke F, Spielhofer P, Schneider H, Kaelin K, Huber M, Dotsch C, Christiansen G, Billeter MA Rescue of measles viruses from cloned DNA EMBO J 1995, 14(23): 5773–5784PubMedGoogle Scholar
  16. 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(2): 910–920PubMedCrossRefGoogle Scholar
  17. 17.
    Spearman C The method of right and wrong cases without Gauss’s formula Br J Psychol 1908, 2: 227–242Google Scholar
  18. 18.
    Cathomen T, Naim HY, Cattaneo R Measles viruses with altered envelope protein cytoplasmic tails gain cell fusion competence J Virol 1998, 72(2): 1224–1234PubMedGoogle Scholar
  19. 19.
    Dethlefsen LA, Prewitt JM, Mendelsohn ML Analysis of tumor growth curves J Natl Cancer Inst 1968, 40(2): 389–405PubMedGoogle Scholar
  20. 20.
    Rencher AC (2002) Methods of Multivariate Analysis 2 edn. John Wiley & Sons, New York, NYGoogle Scholar
  21. 21.
    Phuong LK, Allen C, Peng KW, Giannini C, Greiner S, TenEyck CJ, Mishra PK, Macura SI, Russell SJ, Galanis EC 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(10): 2462–2469PubMedGoogle Scholar
  22. 22.
    Dummer R, Bergh J, Karlsson Y, Horowitz JA, Mulder NH, Huinink DTB, Burg G, Hofbauer G, Osanto S Biological activity and safety of adenoviral vector-expressed wild-type p53 after intratumoral injection in melanoma and breast cancer patients with p53-overexpressing tumors Cancer Gene Ther 2000, 7(7): 1069–1076PubMedCrossRefGoogle Scholar
  23. 23.
    Anderson BD, Nakamura T, Russell SJ, Peng KW High CD46 receptor density determines preferential killing of tumor cells by oncolytic measles virus Cancer Res 2004, 64(14): 4919–4926PubMedCrossRefGoogle Scholar
  24. 24.
    Jemal A, Clegg LX, Ward E, Ries LA, Wu X, Jamison PM, Wingo PA, Howe HL, Anderson RN, Edwards BK (2004) Annual report to the nation on the status of cancer, 1975–2001, with a special feature regarding survival Cancer 101(1): 3–27PubMedCrossRefGoogle Scholar
  25. 25.
    Hortobagyi GN, Ueno NT, Xia W, Zhang S, Wolf JK, Putnam JB, Weiden PL, Willey JS, Carey M, Branham DL et al. Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: a phase I clinical trial J Clin Oncol 2001, 19(14): 3422–3433PubMedGoogle Scholar
  26. 26.
    Yoo GH, Hung MC, Lopez-Berestein G, LaFollette S, Ensley JF, Carey M, Batson E, Reynolds TC, Murray JL Phase I trial of intratumoral liposome E1A gene therapy in patients with recurrent breast and head and neck cancer Clin Cancer Res 2001, 7(5): 1237–1245PubMedGoogle Scholar
  27. 27.
    Nakamura T, Peng KW, Harvey M, Greiner S, Lorimer IA, James CD, Russell SJ: Rescue and propagation of fully retargeted oncolytic measles viruses. Nat Biotechnol 23(2): 209–214, 2005. Epub 2005 Jan 2030Google Scholar
  28. 28.
    Rushmere NK, Knowlden JM, Gee JM: Analysis of the level of mRNA expression of the membrane regulators of complement, CD59, CD55 and CD46, in breast cancer. Int J Cancer 108(6): 930–936, 2004. Write to the Help Desk NCBI | NLM | NIH Department of Health & Human Services Privacy Statement | Freedom of Information Act | DisclaimerGoogle Scholar
  29. 29.
    Oglesby TJ, White D, Tedja I, Liszewski K, Wright L, Van den Bogarde J, Atkinson JP Protection of mammalian cells from complement-mediated lysis by transfection of human membrane cofactor protein and decay-accelerating factor Trans Assoc Am Physicians 1991, 104: 164–172PubMedGoogle Scholar
  30. 30.
    Adams EM, Brown MC, Nunge M, Krych M, Atkinson JP Contribution of the repeating domains of membrane cofactor protein (CD46) of the complement system to ligand binding and cofactor activity J Immunol 1991, 147(9): 3005–3011PubMedGoogle Scholar
  31. 31.
    Niehans GA, Cherwitz DL, Staley NA, Knapp DJ, Dalmasso AP Human carcinomas variably express the complement inhibitory proteins CD46 (membrane cofactor protein), CD55 (decay-accelerating factor), and CD59 (protectin) Am J Pathol 1996, 149(1): 129–142PubMedGoogle Scholar
  32. 32.
    Matsumura A, Ghosh A, Pope GS, Darbre PD Comparative study of oestrogenic properties of eight phytoestrogens in MCF7 human breast cancer cells J Steroid Biochem Mol Biol 2005, 94(5): 431–443PubMedCrossRefGoogle Scholar
  33. 33.
    Boerner JL, Gibson MA, Fox EM, Posner ED, Parsons SJ, Silva CM, Shupnik MA: Estrogen negatively regulates EGF-mediated STAT5 signaling in HER family receptor overexpressing breast cancer cells. Mol Endocrinol 19(11) 2660-2670, 2005PubMedCrossRefGoogle Scholar
  34. 34.
    Leirdal M, Shadidy M, Rosok O, Sioud M Identification of genes differentially expressed in breast cancer cell line SKBR3: potential identification of new prognostic biomarkers Int J Mol Med 2004, 14(2): 217–222PubMedGoogle Scholar
  35. 35.
    Huang H, Groth J, Sossey-Alaoui K, Hawthorn L, Beall S, Geradts J Aberrant expression of novel and previously described cell membrane markers in human breast cancer cell lines and tumors Clin Cancer Res 2005, 11(12): 4357–4364PubMedCrossRefGoogle Scholar
  36. 36.
    Esolen LM, Park SW, Hardwick JM, Griffin DE Apoptosis as a cause of death in measles virus-infected cells J Virol 1995, 69(6): 3955–3958PubMedGoogle Scholar
  37. 37.
    Guadagni F, Ferroni P, Carlini S, Mariotti S, Spila A, Aloe S, D’Alessandro R, Carone MD, Cicchetti A, Ricciotti A et al. A re-evaluation of carcinoembryonic antigen (CEA) as a serum marker for breast cancer: a prospective longitudinal study Clin Cancer Res 2001, 7(8): 2357–2362PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Cari J. McDonald
    • 1
  • Charles Erlichman
    • 2
  • James N. Ingle
    • 2
  • Gabriela A. Rosales
    • 3
  • Cory  Allen
    • 1
  • Suzanne M. Greiner
    • 1
  • Mary E. Harvey
    • 1
  • Paula J. Zollman
    • 1
  • Stephen J. Russell
    • 1
  • Evanthia Galanis
    • 1
    • 2
    • 4
  1. 1.Molecular Medicine ProgramMayo ClinicRochesterUSA
  2. 2.Division of Medical OncologyMayo ClinicRochesterUSA
  3. 3.Department of StatisticsMayo ClinicRochesterUSA
  4. 4.Mayo ClinicRochesterUSA

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