SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on November 14, 2002; DOI 10.1182/blood-2002-07-2195. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-07-2195v1 101/7/2557    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Peng, K.-W. Articles by Russell, S. J. Search for Related Content PubMed PubMed Citation Articles by Peng, K.-W. Articles by Russell, S. J. Related Collections Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 April 2003, Vol. 101, No. 7, pp. 2557-2562 GENE THERAPY Oncolytic measles viruses displaying a single-chain antibody against CD38, a myeloma cell marker Kah-Whye Peng, Kathleen A. Donovan, Urs Schneider, Roberto Cattaneo, John A. Lust, and Stephen J. Russell From the Molecular Medicine Program, Mayo Foundation, Rochester; and Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN. Live attenuated measles virus (MV-Edm) has potent oncolytic activity against myeloma xenografts in mice. Therapy of multiple myeloma, a disseminated plasma cell malignancy, would require systemic administration of the virus. Thus, the virus should ideally be targeted to infect only myeloma cells to minimize collateral damage to normal tissues: viral binding to its natural receptors must be ablated and a new specificity domain that targets entry into myeloma cells be added. This study covers 2 critical steps toward generating such a retargeted virus: (1) a new specificity domain against the plasma cell marker CD38 was constructed in the form of a single-chain antibody (scFv) and (2) display of that scFv on the measles viral envelope glycoprotein successfully redirected virus entry through CD38 expressed on target cells devoid of the natural MV receptors. The anti-CD38 scFv was tethered to the C-terminus of the hemagglutinin (H) glycoprotein of MV-Edm through a Factor Xa protease cleavable linker. Immunoblot analysis demonstrated that the scFv was efficiently incorporated into recombinant viral particles. Replication of MV-CD38 was not hindered by the scFv, reaching titers comparable to MV-Edm. Chinese hamster ovary (CHO) cells were resistant to infection by MV-Edm and MV-CD38. In contrast, CHO cells expressing CD38 became susceptible to infection by MV-CD38 but not MV-Edm. Removal of the displayed scFv rendered MV-CD38 noninfectious on CHO-CD38 cells. Tumorigenicity of CHO-CD38 cells in immunocompromised mice was significantly attenuated by MV-CD38, resulting in enhanced survival of these mice compared with the control group. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. W. H. Ruigrok and D. Gerlier Structure of the measles virus H glycoprotein sheds light on an efficient vaccine PNAS, December 26, 2007; 104(52): 20639 - 20640. [Full Text] [PDF] G. Ungerechts, C. Springfeld, M. E. Frenzke, J. Lampe, P. B. Johnston, W. B. Parker, E. J. Sorscher, and R. Cattaneo Lymphoma Chemovirotherapy: CD20-Targeted and Convertase-Armed Measles Virus Can Synergize with Fludarabine Cancer Res., November 15, 2007; 67(22): 10939 - 10947. [Abstract] [Full Text] [PDF] A. Sarangi, K. Bupp, and M. J. Roth Identification of a retroviral receptor used by an Envelope protein derived by peptide library screening PNAS, June 26, 2007; 104(26): 11032 - 11037. [Abstract] [Full Text] [PDF] K. Hasegawa, T. Nakamura, M. Harvey, Y. Ikeda, A. Oberg, M. Figini, S. Canevari, L. C. Hartmann, and K.-W. Peng The Use of a Tropism-Modified Measles Virus in Folate Receptor-Targeted Virotherapy of Ovarian Cancer. Clin. Cancer Res., October 15, 2006; 12(20): 6170 - 6178. [Abstract] [Full Text] [PDF] M. H. Verheije, T. Wurdinger, V. W. van Beusechem, C. A. M. de Haan, W. R. Gerritsen, and P. J. M. Rottier Redirecting Coronavirus to a Nonnative Receptor through a Virus-Encoded Targeting Adapter J. Virol., February 1, 2006; 80(3): 1250 - 1260. [Abstract] [Full Text] [PDF] L. Heinzerling, V. Kunzi, P. A. Oberholzer, T. Kundig, H. Naim, and R. Dummer Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune responses in vivo and targets interferon-resistant tumor cells Blood, October 1, 2005; 106(7): 2287 - 2294. [Abstract] [Full Text] [PDF] C. Springfeld, V. von Messling, C. A. Tidona, G. Darai, and R. Cattaneo Envelope Targeting: Hemagglutinin Attachment Specificity Rather than Fusion Protein Cleavage-Activation Restricts Tupaia Paramyxovirus Tropism J. Virol., August 15, 2005; 79(16): 10155 - 10163. [Abstract] [Full Text] [PDF] G. P. Horn, S. Vongpunsawad, E. Kornmann, B. Fritz, D. P. Dittmer, R. Cattaneo, and M. Dobbelstein Enhanced Cytotoxicity without Internuclear Spread of Adenovirus upon Cell Fusion by Measles Virus Glycoproteins J. Virol., February 1, 2005; 79(3): 1911 - 1917. [Abstract] [Full Text] [PDF] D. Dingli, K.-W. Peng, M. E. Harvey, P. R. Greipp, M. K. O'Connor, R. Cattaneo, J. C. Morris, and S. J. Russell Image-guided radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal sodium iodide symporter Blood, March 1, 2004; 103(5): 1641 - 1646. [Abstract] [Full Text] [PDF] S. Vongpunsawad, N. Oezgun, W. Braun, and R. Cattaneo 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., January 1, 2004; 78(1): 302 - 313. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020