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, Shunsuke Chikuma, I. Saito, Y. Kanegae, Y. Kawaguchi, A. Kitabatake, T. Uede

Research output: Contribution to journalArticle

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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
Externally publishedYes

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Intra-Articular Injections
Experimental Arthritis
Adenoviridae
Genetic Therapy
Arthritis
Serum
Antigens
Intramuscular Injections
Subcutaneous Injections
Knee Joint
Intravenous Injections
Antibody Formation
Immunoglobulins
Lymphocytes
Injections
Genes
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Successful gene therapy via intraarticular injection of adenovirus vector containing CTLA4IgG in a murine model of type II collagen-induced arthritis. / Ijima, K.; Murakami, M.; Okamoto, H.; Inobe, M.; Chikuma, Shunsuke; Saito, I.; Kanegae, Y.; Kawaguchi, Y.; Kitabatake, A.; Uede, T.

In: Human Gene Therapy, Vol. 12, No. 9, 2001, p. 1063-1077.

Research output: Contribution to journalArticle

Ijima, K, Murakami, M, Okamoto, H, Inobe, M, Chikuma, S, Saito, I, Kanegae, Y, Kawaguchi, Y, Kitabatake, A & Uede, T 2001, 'Successful gene therapy via intraarticular injection of adenovirus vector containing CTLA4IgG in a murine model of type II collagen-induced arthritis', Human Gene Therapy, vol. 12, no. 9, pp. 1063-1077. https://doi.org/10.1089/104303401750214285
Ijima, K. ; Murakami, M. ; Okamoto, H. ; Inobe, M. ; Chikuma, Shunsuke ; Saito, I. ; Kanegae, Y. ; Kawaguchi, Y. ; Kitabatake, A. ; Uede, T. / Successful gene therapy via intraarticular injection of adenovirus vector containing CTLA4IgG in a murine model of type II collagen-induced arthritis. In: Human Gene Therapy. 2001 ; Vol. 12, No. 9. pp. 1063-1077.
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AU - Okamoto, H.

AU - Inobe, M.

AU - Chikuma, Shunsuke

AU - Saito, I.

AU - Kanegae, Y.

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AU - Kitabatake, A.

AU - Uede, T.

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