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CD20-targeted measles virus shows high oncolytic specificity in clinical samples from lymphoma patients independent of prior rituximab therapy

Gene Therapy volume 18, pages 313–317 (2011)Cite this article

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Abstract

New therapeutic modalities for B-cell non-Hodgkin's lymphomas (B-NHL) are needed, especially for relapsing and aggressive subtypes. Toward this end, we previously generated a fully CD20-targeted and armed measles virus, and tested its efficacy in a xenograft model of mantle cell lymphoma (MCL). Here, we quantify its spread in peripheral blood mononuclear cells and/or tissue of patients with different histological subtypes of B-NHL, including splenic marginal zone lymphoma (SMZL). CD20-targeted MV efficiently infects lymphoma cells from SMZL and MCL while sparing most cells in the CD20-negative population, in contrast to the parental vaccine-lineage MV, which infects CD20-positive and CD20-negative cells equally. Rituximab therapy (4–8 months before relapse) did not interfere with the infectivity and specificity of MVgreenHblindantiCD20 in patient lymphoma samples. Thus, CD20-targeted oncolytic virotherapy is likely to be effective after previous antiCD20 therapy.

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References

  1. Cancer Facts & Figures 2009. Amer Cancer Soc 2009: 1–72.

  2. Ruan J, Coleman M, Leonard JP . Management of relapsed mantle cell lymphoma: still a treatment challenge. Oncology (Williston Park, NY) 2009; 23: 683–690.

    Google Scholar 

  3. Galanis E, Hartmann LC, Cliby WA, Long HJ, Peethambaram PP, Barrette BA 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chang J, Zhao X, Wu X, Guo Y, Guo H, Cao J et al. A Phase I study of KH901, a conditionally replicating granulocyte-macrophage colony-stimulating factor: armed oncolytic adenovirus for the treatment of head and neck cancers. Cancer Biol Ther 2009; 8: 676–682.

    Article  CAS  PubMed  Google Scholar 

  5. Hu JCC, Coffin RS, Davis CJ, Graham NJ, Groves N, Guest PJ et al. A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin Cancer Res 2006; 12: 6737–6747.

    Article  CAS  PubMed  Google Scholar 

  6. Vidal L, Pandha HS, Yap TA, White CL, Twigger K, Vile RG et al. A phase I study of intravenous oncolytic reovirus type 3 Dearing in patients with advanced cancer. Clin Cancer Res 2008; 14: 7127–7137.

    Article  CAS  PubMed  Google Scholar 

  7. Russell SJ, Peng KW . Measles virus for cancer therapy. Curr Top Microbiol Immunol 2009; 330: 213–241.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 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 

  9. Bluming AZ, Ziegler JL . Regression of Burkitt's lymphoma in association with measles infection. Lancet 1971; 2: 105–106.

    Article  CAS  PubMed  Google Scholar 

  10. Radecke F, Spielhofer P, Schneider H, Kaelin K, Huber M, Dötsch C et al. Rescue of measles viruses from cloned DNA. EMBO J 1995; 1: 5773–5784.

    Article  Google Scholar 

  11. Hammond AL, Plemper RK, Zhang J, Schneider U, Russell SJ, Cattaneo R . Single-chain antibody displayed on a recombinant measles virus confers entry through the tumor-associated carcinoembryonic antigen. J Virol 2001; 75: 2087–2096.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bucheit AD, Kumar S, Grote DM, Lin Y, von Messling V, Cattaneo RB et al. An oncolytic measles virus engineered to enter cells through the CD20 antigen. Mol Ther 2003; 7: 62–72.

    Article  CAS  PubMed  Google Scholar 

  13. Ungerechts G, Springfeld C, Frenzke ME, Lampe J, Johnston PB, Parker WB et al. Lymphoma chemovirotherapy: CD20-targeted and convertase-armed measles virus can synergize with fludarabine. Cancer Res 2007; 67: 10939–10947.

    Article  CAS  PubMed  Google Scholar 

  14. Naniche D, Varior-Krishnan G, Cervoni F, Wild TF, Rossi B, Rabourdin-Combe C 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 

  15. Vongpunsawad S, Oezgun N, Braun W, Cattaneo R . Selectively receptor-blind measles viruses: identification of residues necessary for SLAM- or CD46-induced fusion and their localization on a new hemagglutinin structural model. J Virol 2004; 78: 302–313.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Grillo-López AJ, White CA, Varns C, Shen D, Wei A, McClure A et al. Overview of the clinical development of rituximab: first monoclonal antibody approved for the treatment of lymphoma. Semin Oncol 1999; 26: 66–73.

    PubMed  Google Scholar 

  17. Ungerechts G, Frenzke ME, Yaiw KC, Miest TS, Johnston PB, Cattaneo R . Mantle cell lymphoma salvage regimen: synergy between a reprogrammed oncolytic virus and two chemotherapeutics. Gene Ther 2010, but doi:10.1038/gt.2010.103.

  18. Cattaneo R, Miest T, Shashkova EV, Barry MA . Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded. Nat Rev Microbiol 2008; 6: 529–540.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dingli D, Peng K-W, Harvey ME, Greipp PR, O’Connor MK, Cattaneo R 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 

  20. Jaffe ES . The 2008 WHO classification of lymphomas: implications for clinical practice and translational research. Hematology Am Soc Hematol Educ Program 2009: 523–531.

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Acknowledgements

This work was supported by a grant of the Alliance for Cancer Gene Therapy and NIH grant R01 CA139389. We thank the Mayo Clinic Flow Cytometry Core, Mary Stenson and Tammy Rattle for providing clinical samples, and Mary Bennett for excellent secretarial assistance. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Authors and Affiliations

  1. Department of Molecular Medicine, and Virology and Gene Therapy Track,

    K-C Yaiw, T S Miest, M Frenzke & R Cattaneo

  2. Mayo Clinic College of Medicine, Rochester, MN, USA

    K-C Yaiw, T S Miest, M Frenzke & R Cattaneo

  3. Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA

    M Timm

  4. Department of Hematology, Mayo Clinic College of Medicine, Rochester, MN, USA

    P B Johnston

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  1. K-C Yaiw
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  2. T S Miest
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  6. R Cattaneo
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Correspondence to R Cattaneo.

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Patent applications on which RC is an inventor have been licensed to NISCO Inc., Mayo has an equity position in NISCO; Mayo has not yet received royalties from products developed by the company, but may receive these in the future.

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Yaiw, KC., Miest, T., Frenzke, M. et al. CD20-targeted measles virus shows high oncolytic specificity in clinical samples from lymphoma patients independent of prior rituximab therapy. Gene Ther 18, 313–317 (2011). https://doi.org/10.1038/gt.2010.150

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  • DOI: https://doi.org/10.1038/gt.2010.150

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