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 language | English |
|---|---|
| Pages (from-to) | 1063-1077 |
| Number of pages | 15 |
| Journal | Human Gene Therapy |
| Volume | 12 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2001 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Successful gene therapy via intraarticular injection of adenovirus vector containing CTLA4IgG in a murine model of type II collagen-induced arthritis
AU - Ijima, K.
AU - Murakami, M.
AU - Okamoto, H.
AU - Inobe, M.
AU - Chikuma, Shunsuke
AU - Saito, I.
AU - Kanegae, Y.
AU - Kawaguchi, Y.
AU - Kitabatake, A.
AU - Uede, T.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034926901&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034926901&partnerID=8YFLogxK
U2 - 10.1089/104303401750214285
DO - 10.1089/104303401750214285
M3 - Article
C2 - 11399228
AN - SCOPUS:0034926901
VL - 12
SP - 1063
EP - 1077
JO - Human Gene Therapy
JF - Human Gene Therapy
SN - 1043-0342
IS - 9
ER -