Nondepleting anti-CD4 antibody treatment prolongs lung-directed E1-deleted adenovirus-mediated gene expression in rats

Hum Gene Ther. 1996 Dec 1;7(18):2273-9. doi: 10.1089/hum.1996.7.18-2273.


E1-deleted adenoviral vectors are efficient vectors for somatic cell gene therapy, but transgene expression is limited in part by a cytotoxic T cell response directed against virally transduced cells. Moreover, the development of a neutralizing antibody response limits secondary gene transfer with these vectors. Therapy with a depleting anti-CD4 antibody permits prolonged transgene expression in the lung and liver of mice. Furthermore, transient depletion of CD4+ lymphocytes blocks neutralizing antibody production and therefore allows repeat administration and expression of E1-deleted recombinant adenovirus. In this study, we investigated the efficacy of a novel nondepleting anti-CD4 antibody (RIB 5/2) in a model of lung-directed gene therapy in outbred rats. Treatment with RIB 5/2 permitted prolonged reporter gene expression and reduced adenovirus-induced peribronchial and alveolar inflammation in the lung. Moreover administration of RIB 5/2 blocked the development of an anti-adenoviral neutralizing antibody response in the lung and permitted secondary administration and expression of a recombinant adenovirus. These data support the role of immunomodulation in prolonging in vivo transgene expression by recombinant adenovirus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenovirus E1 Proteins
  • Adenoviruses, Human / genetics*
  • Adenoviruses, Human / immunology
  • Animals
  • Antibodies, Monoclonal*
  • Antibodies, Viral / analysis
  • Antibodies, Viral / blood
  • Bronchoalveolar Lavage Fluid / immunology
  • CD4 Antigens / immunology*
  • Gene Expression Regulation / immunology*
  • Genes, Reporter / genetics
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics*
  • Genetic Vectors / immunology
  • Humans
  • Luciferases / genetics
  • Lung / immunology*
  • Lung / metabolism
  • Lymphocyte Subsets
  • Male
  • Neutralization Tests
  • Rats
  • Rats, Sprague-Dawley
  • T-Lymphocytes, Cytotoxic / immunology
  • beta-Galactosidase / genetics


  • Adenovirus E1 Proteins
  • Antibodies, Monoclonal
  • Antibodies, Viral
  • CD4 Antigens
  • Luciferases
  • beta-Galactosidase