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Human Gene Therapy
Preferential Survival of CD4+ T Lymphocytes Engineered with Anti-Human Immunodeficiency Virus (HIV) Genes in HIV-Infected Individuals
To cite this article:
Richard A. Morgan, Robert Walker, Charles S. Carter, Ven Natarajan, Jorge A. Tavel, Chris Bechtel, Betsy Herpin, Linda Muul, Zhili Zheng, Shyla Jagannatha, Bruce A. Bunnell, Vicki Fellowes, Julia A. Metcalf, Randy Stevens, Michael Baseler, Susan F. Leitman, Elizabeth J. Read, R. Michael Blaese, H. Clifford Lane.
Human Gene Therapy.
September 2005,
16(9): 1065-1074.
doi:10.1089/hum.2005.16.1065.
Published in Volume: 16 Issue 9: September 8, 2005
Richard A. Morgan National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892. Robert Walker National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Charles S. Carter Clinical Center, National Institutes of Health, Bethesda, MD 20892. Ven Natarajan SAIC-Frederick, Cancer Research and Development Center, Frederick, MD 21702. Dr. Jorge A. Tavel National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Chris Bechtel National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Betsy Herpin National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Linda Muul National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892. Zhili Zheng National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892. Shyla Jagannatha SAIC-Frederick, Cancer Research and Development Center, Frederick, MD 21702. Bruce A. Bunnell National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892. Vicki Fellowes Clinical Center, National Institutes of Health, Bethesda, MD 20892. Julia A. Metcalf Clinical Center, National Institutes of Health, Bethesda, MD 20892. Randy Stevens SAIC-Frederick, Cancer Research and Development Center, Frederick, MD 21702. Michael Baseler SAIC-Frederick, Cancer Research and Development Center, Frederick, MD 21702. Susan F. Leitman Clinical Center, National Institutes of Health, Bethesda, MD 20892. Elizabeth J. Read Clinical Center, National Institutes of Health, Bethesda, MD 20892. R. Michael Blaese National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892. H. Clifford Lane National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. The present study examined the safety and relative in vivo survival of genetically engineered CD4+ T lymphocytes in human immunodeficiency virus (HIV)-infected individuals. Ten pairs of identical twins discordant for HIV infection were recruited, with the uninfected twin serving as the lymphocyte donor. Ten subjects were treated with a total of 19 separate infusions of retroviral vector-transduced CD4+ enriched T cells. Control (neo gene) or anti-HIV gene (antisense trans-activation response [TAR] element and/or trans-dominant Rev)-engineered lymphocytes were monitored in peripheral blood for 3 years, using a vector-specific PCR assay. Data from 9 of the 10 patients (15 of the 19 infusions) demonstrated preferential survival of CD4+ lymphocytes containing the anti-HIV gene(s) in the immediate weeks after infusion. In six of six patients studied long term (>100 weeks), only T cells containing the anti-HIV genes were consistently detected. In addition, a marked survival advantage of anti-HIV gene-containing T cells was observed in a patient treated during a period of high viral load. Thus, these data strongly support the hypothesis that anti-HIV genes afford a survival advantage to T cells and potential benefit to HIV-1+ individuals.  This paper was cited by:Lentiviral Vector Design for Optimal T Cell Receptor Gene Expression in the Transduction of Peripheral Blood Lymphocytes and Tumor-Infiltrating Lymphocytes Stephanie Jones, Peter D. Peng, Shicheng Yang, Cary Hsu, Cyrille J. Cohen, Yangbing Zhao, John Abad, Zhili Zheng, Steven A. Rosenberg, Richard A. Morgan Human Gene Therapy. Jun 2009, Vol. 20, No. 6: 630-640 Abstract | Full Text PDF | Reprints & PermissionsPhase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells Ronald T Mitsuyasu, Thomas C Merigan, Andrew Carr, Jerome A Zack, Mark A Winters, Cassy Workman, Mark Bloch, Jacob Lalezari, Stephen Becker, Lorna Thornton, Bisher Akil, Homayoon Khanlou, Robert Finlayson, Robert McFarlane, Don E Smith, Roger Garsia, David Ma, Matthew Law, John M Murray, Christof von Kalle, Julie A Ely, Sharon M Patino, Alison E Knop, Philip Wong, Alison V Todd, Margaret Haughton, Caroline Fuery, Janet L Macpherson, Geoff P Symonds, Louise A Evans, Susan M Pond, David A Cooper Nature Medicine. Apr 2009, Vol. 15, No. 3: 285-292 CrossRef Generation of T Lineage Cells from Human Embryonic Stem Cells in a Feeder Free System Zoran Galić, Scott G. Kitchen, Aparna Subramanian, Greg Bristol, Matthew D. Marsden, Arumugam Balamurugan, Amelia Kacena, Otto Yang, Jerome A. Zack Stem Cells. Feb 2009, Vol. 27, No. 1: 100-107 CrossRef Fusion of Epstein-Barr Virus Nuclear Antigen-1-Derived Glycine–Alanine Repeat to Trans-Dominant HIV-1 Gag Increases Inhibitory Activities and Survival of Transduced Cells In Vivo Diana Hammer, , Jens Wild, Christine Ludwig, Benedikt Asbach, Frank Notka, Ralf Wagner Human Gene Therapy. Jun 2008, Vol. 19, No. 6: 622-634 Abstract | Full Text PDF | Reprints & PermissionsGenetic therapies against HIV John J Rossi, Carl H June, Donald B Kohn Nature Biotechnology. Jan 2008, Vol. 25, No. 12: 1444-1454 CrossRef RNA interference against viruses: strike and counterstrike Joost Haasnoot, Ellen M Westerhout, Ben Berkhout Nature Biotechnology. Jan 2008, Vol. 25, No. 12: 1435-1443 CrossRef Transfer of Autologous Gene-modified T Cells in HIV-infected Patients with Advanced Immunodeficiency and Drug-resistant Virus Jan van Lunzen, Tobias Glaunsinger, Ingrid Stahmer, Volker von Baehr, Christopher Baum, Andrea Schilz, Klaus Kuehlcke, Sonja Naundorf, Holger Martinius, Felix Hermann, Tsanan Giroglou, Sebastian Newrzela, Ingrid Müller, Francis Brauer, Gunda Brandenburg, Alexander Alexandrov, Dorothee von Laer Molecular Therapy. Apr 2007 CrossRef Adoptive transfer of syngeneic T cells in HIV-1 discordant twins indicates rapid regulation of T-cell homeostasis Christian Hoffmann, Hans-Juergen Stellbrink, Thomas Dielschneider, Olaf Degen, Albrecht Stoehr, Heribert Knechten, Eva Wolf, Jan van Lunzen British Journal of Haematology. Mar 2007, Vol. 136, No. 4: 641-648 CrossRef Novel mfgl2 Antisense Plasmid Inhibits Murine fgl2 Expression and Ameliorates Murine Hepatitis Virus Type 3-Induced Fulminant Hepatitis in BALB/cJ Mice Chuanlong Zhu, Yi Sun, Xiaoping Luo, Weiming Yan, Dong Xi, Qin Ning Human Gene Therapy. Jul 2006, Vol. 0, No. 0: 060801084750008 CrossRef Gene-Based Immunotherapy for Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome Boro Dropulic, Carl H. June Human Gene Therapy. Jul 2006, Vol. 0, No. 0: 060801084750012 CrossRef Gene therapy for HIV infection: what does it need to make it work? Dorothee von Laer, Susanne Hasselmann, Klaus Hasselmann The Journal of Gene Medicine. Jul 2006, Vol. 8, No. 6: 658-667 CrossRef Novel mfgl2 Antisense Plasmid Inhibits Murine fgl2 Expression and Ameliorates Murine Hepatitis Virus Type 3-Induced Fulminant Hepatitis in BALB/cJ Mice Chuanlong Zhu, Yi Sun, Xiaoping Luo, Weiming Yan, Dong Xi, Qin Ning Human Gene Therapy. Jun 2006, Vol. 17, No. 6: 589-600 Abstract | Full Text PDF | Reprints & PermissionsGene-Based Immunotherapy for Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome Boro Dropulic, Carl H. June Human Gene Therapy. Jun 2006, Vol. 17, No. 6: 577-588 Abstract | Full Text PDF | Reprints & Permissions |
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