PMID: 9188602Jul 1, 1997Paper

Long-lasting adenovirus transgene expression in mice through neonatal intrathymic tolerance induction without the use of immunosuppression

Journal of Virology
R P DeMatteoJ F Markmann

Abstract

The major barrier to the clinical application of adenovirus gene therapy for diseases that require stable transgene expression is the immunogenicity of recombinant adenovirus, which ordinarily limits the duration of its effects to a period of about 2 weeks. We postulated that tolerance to adenovirus could be induced and transgene expression could be prolonged if T lymphocytes underwent thymic selection in the presence of adenovirus antigens. Mice were inoculated in the thymus with a recombinant adenovirus containing the lacZ marker gene during the neonatal period at a time before T-cell maturation had occurred. When the virus was administered intravenously to these mice in adulthood, they were found to have an impaired adenovirus-specific cytotoxic T-lymphocyte response which allowed prolonged hepatic lacZ expression, for up to 260 days. The ability to achieve unresponsiveness to a recombinant adenovirus after inoculation of the thymus in neonates extends the paradigm of intrathymic tolerance induction. Furthermore, this model will enable the study of stable adenovirus transgene expression in vivo without the use of immunosuppression and ultimately may have clinical utility.

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Citations

Oct 6, 1998·Human Gene Therapy·N Ferry, J M Heard
Sep 10, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·George MillerRonald P DeMatteo
Feb 21, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·George MillerRonald P Dematteo
Nov 18, 2003·Immunological Reviews·Dolca Thomas, Manikkam Suthanthiran
Oct 19, 2005·Gene Therapy·R AlbaM Chillon
Mar 12, 2005·Human Gene Therapy·Dan H Barouch, Gary J Nabel
Apr 24, 2007·Lab Animal·Teresa de la CuevaDaniel Rubio
Sep 11, 2004·Viral Immunology·Huibi CaoJim Hu
Mar 26, 2003·Clinical and Experimental Immunology·S FerrariE Alton
Apr 20, 2004·International Journal of Cancer. Journal International Du Cancer·George MillerRonald P DeMatteo
Feb 26, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Venu G PillarisettyRonald P DeMatteo
Jan 10, 2012·The Journal of Gene Medicine·Gaëlle GottrandGilles Marodon
Feb 8, 2003·DNA and Cell Biology·Chooi May LaiP Elizabeth Rakoczy
Mar 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·George MillerRonald P DeMatteo
Nov 4, 2000·Expert Opinion on Investigational Drugs·E Imai, Y Isaka
Jan 4, 2006·The Journal of Gene Medicine·Elena FedorovaG Luca Gusella
Sep 13, 2019·The Journal of Allergy and Clinical Immunology·Marie PouzollesValérie S Zimmermann
May 10, 2003·Cancer Immunology, Immunotherapy : CII·George MillerRonald P DeMatteo
Oct 6, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·G S LipshutzK M Gaensler
Apr 20, 2004·Critical Reviews in Oncology/hematology·Frederik H E SchagenRob C Hoeben
Apr 27, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Simon N WaddingtonJesus Prieto
Feb 14, 1998·Kidney International·E Imai, Y Isaka

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