Successful gene therapy via intraarticular injection of adenovirus vector containing CTLA4IgG in a murine model of type II collagen-induced arthritis

K. Ijima, M. Murakami, H. Okamoto, M. Inobe, S. Chikuma, I. Saito, Y. Kanegae, Y. Kawaguchi, A. Kitabatake, T. Uede

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Abstract

We previously constructed an adenovirus vector carrying a gene encoding a soluble form of fusion protein, consisting of the extracellular portion of cytotoxic lymphocyte antigen 4 (CTLA4) and the Fc portion of human immunoglobulin G1 (Adex1CACTLA4IgG). Murine type II collagen-induced arthritis (CIA) was treated with Adex1CACTLA4IgG. A single intraarticular injection of 1 × 105 PFU was able to support serum CTLA4IgG at more than 10 μg/ml for at least 12 weeks and was able to inhibit the CIA clinically and histo-logically. In contrast, intravenous, intramuscular, or subcutaneous injection of 1 × 105 PFU was unable to support a significant level of serum CTLA4IgG and thus was unable to inhibit the development of arthritis. Thus, we demonstrated that (1) a low-dose intraarticular injection of Adex1CACTLA4IgG was effective in delaying the onset of CIA and reducing the severity of arthritis; (2) an intraarticular (knee joint) injection of Adex1CACTLA4IgG effectively blocked the development of arthritis in distal paws; (3) the inhibitory effect of Adex1CACTLA4IgG lasted at least up to 20 weeks; (4) although serum CTLA4IgG at more than 10 μg/ml persisted for at least 12 weeks, mice treated by intraarticular injection of Adex1CACTLA4IgG were not an-ergic to adenovirus and were able to mount antibody responses against various antigens.

Original languageEnglish
Pages (from-to)1063-1077
Number of pages15
JournalHuman Gene Therapy
Volume12
Issue number9
DOIs
Publication statusPublished - 2001 Aug 9
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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