Transient immunosuppression with deoxyspergualin improves longevity of transgene expression and ability to readminister adenoviral vector to the mouse lung

Human Gene Therapy
J M Kaplan, A E Smith

Abstract

Animal studies have suggested that the clinical usefulness of recombinant adenoviruses (Ad) as vectors for therapeutic gene delivery may be limited by their immunogenicity. Neutralizing antibodies elicited by capsid proteins reduce the efficiency of vector readministration whereas cytotoxic T lymphocytes (CTLs) directed against viral proteins and/or immunogenic transgene products expressed by transfected cells have the potential to limit persistence of expression. In this study, transient administration of the novel immunosuppressant deoxyspergualin (DSG) was found to inhibit the development of both humoral and cell-mediated immune responses against Ad vector delivered intranasally. DSG treatment of primed mice previously exposed to wild-type Ad impaired the development of antibodies in response to a secondary and even tertiary challenge with Ad vector. As a result, improved gene transfer was obtained upon subsequent administration of a beta-galactosidase (beta-Gal)-encoding Ad vector. Short-term administration of DSG also depressed the activation of CD4+ and CD8+ T lymphocytes as assessed by measurement of antigen-specific proliferation and CTL activity, respectively. The marked suppression of CTL activity against Ad vector in...Continue Reading

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Citations

Apr 20, 2004·Critical Reviews in Oncology/hematology·Frederik H E SchagenRob C Hoeben
Jan 20, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Terence R FlotteJim Hu
May 3, 2001·Journal of Virology·P W ZoltickJ M Wilson
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Jul 2, 2005·Expert Opinion on Investigational Drugs·W W Zhang
Jul 2, 2005·Expert Opinion on Investigational Drugs·T A Smith
Feb 28, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Patricia YotndaMalcolm K Brenner
Apr 20, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Patricia YotndaM K Benner
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Mar 29, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·A I KuzminR C Eisensmith
Apr 17, 2002·Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery·Ian N JacobsTimothy Crombleholme
Oct 19, 2005·Gene Therapy·R AlbaM Chillon
Oct 20, 2000·The Journal of General Virology·W C Russell
May 18, 1999·The Journal of Allergy and Clinical Immunology·H KurataK Arai

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