       Document 0758
 DOCN  M9620758
 TI    Recombinant IL-12 prevents formation of blocking IgA antibodies to
       recombinant adenovirus and allows repeated gene therapy to mouse lung
       [see comments]
 DT    9602
 AU    Yang Y; Trinchieri G; Wilson JM; Institute for Human Gene Therapy,
       Wistar Institute, University of; Pennsylvania Medical Center,
       Philadelphia 19104-4268, USA.
 SO    Nat Med. 1995 Sep;1(9):890-3. Unique Identifier : AIDSLINE MED/96071593
 CM    Comment in: Nat Med 1995 Sep;1(9):887-9
 AB    Enthusiasm for the use of recombinant adenoviruses in gene therapy has
       been tempered by the problematic immune responses that develop to the
       virus and virus-infected cells. Humoral immune responses to the input
       viral proteins generate neutralizing antibodies that thwart attempts to
       effectively administer the therapy more than once. Previous studies in
       murine models of gene therapy for cystic fibrosis (CF) have shown that
       the formation of adenoviral antibodies of the IgA subtype, a process
       that is dependent on T helper cells of the TH2 subset, contributes to a
       block in gene transfer that occurs following a second administration of
       virus. We show in this report that coadministration of interferon-gamma
       (IFN-gamma) (or interleukin-12, which activates TH1 cells to secrete
       IFN-gamma) with the recombinant adenovirus into the airway of C57BL/6
       mice diminishes the activation of TH2 cells and formation of
       neutralizing antibody, allowing for efficient readministration of
       recombinant virus. This suggests a strategy for gene therapy of CF in
       which administration of a short-acting immune modulator at the time of
       gene therapy may be sufficient to overcome the problems of humoral
       immunity.
 DE    Adenoviridae/GENETICS/*IMMUNOLOGY  Animal  Antibodies,
       Monoclonal/IMMUNOLOGY/PHARMACOLOGY  Antibodies,
       Viral/*BIOSYNTHESIS/IMMUNOLOGY  Antigens, CD4/IMMUNOLOGY  Biological
       Response Modifiers/PHARMACOLOGY/*THERAPEUTIC USE  Defective
       Viruses/GENETICS/*IMMUNOLOGY  *Gene Therapy  Genetic
       Vectors/GENETICS/*IMMUNOLOGY  IgA/*BIOSYNTHESIS/IMMUNOLOGY  Immunologic
       Memory  *Immunosuppression  Interferon-gamma, Recombinant/*THERAPEUTIC
       USE  Interleukin-12/PHARMACOLOGY/SECRETION/*THERAPEUTIC USE
       Lung/IMMUNOLOGY/VIROLOGY  Lymphocyte Cooperation/DRUG EFFECTS
       Lymphocyte Transformation  Mice  Mice, Inbred C57BL  Recombinant
       Proteins/PHARMACOLOGY/THERAPEUTIC USE  Support, Non-U.S. Gov't  Support,
       U.S. Gov't, P.H.S.  Th1 Cells/DRUG EFFECTS/SECRETION  Th2 Cells/DRUG
       EFFECTS/*IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

