Persistent and secondary adenovirus-mediated hepatic gene expression using adenovirus vector containing CTLA4IgG

Hum Gene Ther. 1998 Aug 10;9(12):1739-45. doi: 10.1089/hum.1998.9.12-1739.


Adenovirus vectors can transfer recombinant genes efficiently into a wide variety of cells in vivo, but have serious limitations: gene expression is transient and secondary gene transfer is inefficient or impossible because of cellular and humoral immune responses against adenovirus-transduced cells. To solve these limitations, we have constructed an adenovirus vector, Adex1CACTLA4IgG, that expresses CTLA4IgG molecules. After in vivo administration of Adex1CACTLA4IgG (9.0 x 10(9) PFU), the peak level of serum CTLA4IgG was 29.8 mg/ml on day 4. The serum CTLA4IgG concentration gradually fell but was still 5.7 mg/ml on day 90. However, the serum concentration of CTLA4IgG was elevated after a second administration of Adex1CACTLA4IgG. The production of antibody against adenovirus was completely prevented after treatment with Adex1CACTLA4IgG. In addition, coadministration of Adex1CALacZ with Adex1CACTLA4IgG induced persistent hepatic expression of beta-Gal molecules, while administration of Adex1CALacZ alone induced transient expression of beta-Gal molecules. More importantly, on day 160 a secondary challenge with Adex1CALacZ was possible in mice treated with Adex1CALacZ plus Adex1CACTLA4IgG. Thus, we have demonstrated that (1) gene expression of a recombinant adenovirus, Adex1CACTLA4IgG, is persistent in liver and secondary administration of this adenovirus is possible, (2) coadministration of Adex1CACTLA4IgG virus with another adenovirus, AdexCALacZ, prolongs AdexCALacZ-mediated gene expression, and (3) Adex1CACTLA4IgG is useful for secondary challenge with Adex1CALacZ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Adenoviridae / genetics*
  • Adenoviridae / immunology
  • Animals
  • Antibodies, Viral / biosynthesis
  • Antigens, CD
  • Antigens, Differentiation / administration & dosage
  • Antigens, Differentiation / blood
  • Antigens, Differentiation / genetics*
  • CTLA-4 Antigen
  • Female
  • Gene Expression*
  • Genetic Vectors*
  • Immunoconjugates*
  • Immunoglobulin G / administration & dosage
  • Immunoglobulin G / blood
  • Immunoglobulin G / genetics*
  • Liver / metabolism*
  • Mice
  • Mice, Inbred CBA


  • Antibodies, Viral
  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Immunoglobulin G
  • Abatacept