Genetically engineered attenuated measles virus specifically infects and kills primary multiple myeloma cells Free

Abstract

The applicability of cytoreductive treatment of malignant diseases using recombinant viruses strongly depends on specific recognition of surface receptors to target exclusively neoplastic cells. A recently generated monoclonal antibody (mAb), Wue-1, specifically detects CD138 multiple myeloma (MM) cells. In this study, a haemagglutinin (H) protein that was receptor-blinded (i.e. did not bind to CD46 and CD150) was genetically re-engineered by fusing it to a single-chain antibody fragment (scFv) derived from the Wue-1 mAb open reading frame (scFv-Wue), resulting in the recombinant retargeted measles virus (MV)-Wue. MV-Wue efficiently targeted and fully replicated in primary MM cells, reaching titres similar to those seen with non-retargeted viruses. In agreement with its altered receptor specificity, infection of target cells was no longer dependent on CD150 or CD46, but was restricted to cells that had been labelled with Wue-1 mAb. Importantly, infection with MV-Wue rapidly induced apoptosis in CD138 malignant plasma cell targets. MV-Wue is the first fully retargeted MV using the restricted interaction between Wue-1 mAb and primary MM cells specifically to infect, replicate in and deplete malignant plasma cells.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.007302-0
2009-03-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/90/3/693.html?itemId=/content/journal/jgv/10.1099/vir.0.007302-0&mimeType=html&fmt=ahah

References

  1. Cattaneo R., Miest T., Shashkova E. V., Barry M. A. 2008; Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded. Nat Rev Microbiol 6:529–540 [CrossRef]
    [Google Scholar]
  2. Dingli D., Peng K.-W., Harvey M. E., Greipp P. R., O'Connor M. K., Cattaneo R., Morris J. C., Russell S. J. 2004; Image-guided radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal sodium iodide symporter. Blood 103:1641–1646 [CrossRef]
    [Google Scholar]
  3. Dörig R. E., Marcil A., Chopra A., Richardson C. D. 1993; The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell 75:295–305 [CrossRef]
    [Google Scholar]
  4. Duprex W. P., McQuaid S., Hangartner L., Billeter M. A., Rima B. K. 1999; Observation of measles virus cell-to-cell spread in astrocytoma cells by using a green fluorescent protein-expressing recombinant virus. J Virol 73:9568–9575
    [Google Scholar]
  5. Greiner A., Neumann M., Stingl S., Wassink S., Marx A., Riechert F., Müller-Hermelink H. K. 2000a; Characterization of Wue-1, a novel monoclonal antibody that stimulates the growth of plasmacytoma cell lines. Virchows Arch 437:372–379 [CrossRef]
    [Google Scholar]
  6. Greiner A., Muller K. B., Hess J., Pfeffer K., Müller-Hermelink H. K., Wirth T. 2000b; Up-regulation of BOB.1/OBF.1 expression in normal germinal center B cells and germinal center-derived lymphomas. Am J Pathol 156:501–507 [CrossRef]
    [Google Scholar]
  7. Grote D., Russell S. J., Cornu T. I., Cattaneo R., Vile R., Poland G. A., Fielding A. K. 2001; Live attenuated measles virus induces regression of human lymphoma xenografts in immunodeficient mice. Blood 97:3746–3754 [CrossRef]
    [Google Scholar]
  8. Harris N. L., Jaffe E. S., Diebold J., Flandrin G., Muller-Hermelink H. K., Vardiman J., Lister T. A., Bloomfield C. D. 2000; The World Health Organization classification of hematological malignancies report of the Clinical Advisory Committee Meeting. Airlie House; Virginia: November 1997 Mod Pathol 13:193–207 [CrossRef]
    [Google Scholar]
  9. Harrison S. J., Cook G. 2005; Immunotherapy in multiple myeloma – possibility or probability?. Br J Haematol 130:344–362 [CrossRef]
    [Google Scholar]
  10. Iankov I. D., Blechacz B., Liu C., Schmeckpeper J. D., Tarara J. E., Federspiel M. J., Caplice N., Russell S. J. 2007; Infected cell carriers: a new strategy for systemic delivery of oncolytic measles viruses in cancer virotherapy. Mol Ther 15:114–122 [CrossRef]
    [Google Scholar]
  11. Kärber G. 1931; Beitrag zur kollektiven Behandlung pharmakologischer Reihenversuche. Naunyn-Schmiedebergs Arch Pharmakol 162:480–483 (in German [CrossRef]
    [Google Scholar]
  12. Kondo E., Topp M. S., Kiem H. P., Obata Y., Morishima Y., Kuzushima K., Tanimoto M., Harada M., Takahashi T., Akatsuka Y. 2002; Efficient generation of antigen-specific cytotoxic T cells using retrovirally transduced CD40-activated B cells. J Immunol 169:2164–2171 [CrossRef]
    [Google Scholar]
  13. Leonard V. H. J., Sinn P. L., Hodge G., Miest T., Deveaux P., Oezguen N., Braun W., McCray P. B. Jr, McChesney M. B., Cattaneo R. 2008; Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed. J Clin Invest 118:2448–2458
    [Google Scholar]
  14. Nakamura T., Russell S. J. 2004; Oncolytic measles viruses for cancer therapy. Expert Opin Biol Ther 4:1685–1692 [CrossRef]
    [Google Scholar]
  15. Nakamura T., Peng K. W., Harvey M., Greiner S., Lorimer I. A., James C. D., Russell S. J. 2005; Rescue and propagation of fully retargeted oncolytic measles viruses. Nat Biotechnol 23:209–214 [CrossRef]
    [Google Scholar]
  16. Naniche D., Varior-Krishnan G., Cervoni F., Wild T. F., Rossi B., Rabourdin-Combe C., Gerlier D. 1993; Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus. J Virol 67:6025–6032
    [Google Scholar]
  17. Ong H. T., Hasegawa K., Dietz A. B., Russell S. J., Peng K.-W. 2007; Evaluation of T cells as carriers for systemic measles virotherapy in the presence of antiviral antibodies. Gene Ther 14:324–333 [CrossRef]
    [Google Scholar]
  18. Parato K. A., Senger D., Forsyth P. A. J., Bell J. C. 2005; Recent progress in the battle between oncolytic viruses and tumours. Nat Rev Cancer 5:965–976 [CrossRef]
    [Google Scholar]
  19. Radecke F., Spielhofer P., Schneider H., Kaelin K., Huber M., Dötsch C., Christiansen G., Billeter M. A. 1995; Rescue of measles viruses from cloned DNA. EMBO J 14:5773–5784
    [Google Scholar]
  20. Spearman C. 1908; The method of right and wrong cases (constant stimuli) without Gauss's formulae. Br J Psychol 2:227–242
    [Google Scholar]
  21. Tatsuo H., Ono N., Tanaka K., Yanagi Y. 2000; SLAM (CDw150) is a cellular receptor for measles virus. Nature 406:893–897 [CrossRef]
    [Google Scholar]
  22. Treon S. P., Raje N., Anderson K. C. 2000; Immunotherapeutic strategies for the treatment of plasma cell malignancies. Semin Oncol 27:598–613
    [Google Scholar]
  23. Yanagi Y., Takeda M., Ohno S. 2006; Measles virus: cellular receptors, tropism and pathogenesis. J Gen Virol 87:2767–2779 [CrossRef]
    [Google Scholar]
  24. Zuniga A., Wang Z., Liniger M., Hangartner L., Caballero M., Pavlovic J., Wild P., Viret J. F., Glueck R. other authors 2007; Attenuated measles virus as a vaccine vector. Vaccine 25:2974–2983 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.007302-0
Loading
/content/journal/jgv/10.1099/vir.0.007302-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed