| 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 x 10(5) PFU was able to support serum CTLA4IgG at more than 10 microg/ml for at least 12 weeks and was able to inhibit the CIA clinically and histologically. In contrast, intravenous, intramuscular, or subcutaneous injection of 1 x 10(5) 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 microg/ml persisted for at least 12 weeks, mice treated by intraarticular injection of Adex1CACTLA4IgG were not anergic to adenovirus and were able to mount antibody responses against various antigens. |
| Authors | K Ijima, M Murakami, H Okamoto, M Inobe, S Chikuma, I Saito, Y Kanegae, Y Kawaguchi, A Kitabatake, T Uede
(Affiliation: Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, 060-0815 Sapporo, Japan.)
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| Journal | Human gene therapy
(Hum Gene Ther)
Vol. 12
Issue 9
Pg. 1063-77
(Jun 10 2001)
ISSN: 1043-0342 United States |
| PMID | 11399228
(Publication Type: Comparative Study, Journal Article)
|
| Chemical References |
- Antigens, CD
- Antigens, Differentiation
- Immunoconjugates
- Immunoglobulin Fc Fragments
- Immunoglobulin G
- abatacept
- cytotoxic T-lymphocyte antigen 4
- Collagen
|
| Topics |
- Adenoviridae
(genetics)
- Animals
- Antigens, CD
- Antigens, Differentiation
(administration & dosage, biosynthesis, genetics, therapeutic use)
- Arthritis, Experimental
(genetics, immunology, pathology, therapy)
- Collagen
(administration & dosage, immunology)
- Disease Progression
- Female
- Gene Therapy
(methods)
- Genetic Vectors
(administration & dosage)
- Immunity, Natural
(genetics)
- Immunoconjugates
- Immunoglobulin Fc Fragments
(administration & dosage, biosynthesis, genetics)
- Immunoglobulin G
(administration & dosage, biosynthesis, genetics, therapeutic use)
- Injections, Intra-Articular
- Injections, Intramuscular
- Injections, Intravenous
- Injections, Subcutaneous
- Mice
- Mice, Inbred DBA
- Severity of Illness Index
|
