Abstract
In psoriasis, CD28/B7 costimulatory molecules are well characterized. Here, using the severe combined immunodeficient (SCID) mouse-psoriasis xenograft model, we report therapeutic efficacy of a humanized anti-CD28 monoclonal antibody (FR255734; Astellas Pharmaceuticals Inc., Tokyo, Japan). Transplanted psoriasis plaques on the SCID mouse were treated weekly for 4 weeks with intraperitoneal injections of FR255734 at 10, 3, and 1-mg kg-1 doses. Groups treated with doses of 10 and 3 mg kg-1had significant thinning of the epidermis and reduced HLA-DR-positive lymphocytic infiltrates. The length of the rete pegs changed from 415.2±59.6 to 231.4±40.4 μm (P<0.005) in the 10-mg kg-1 group, and from 323.4±69.6 to 237.5±73.6 μm in the 3-mg kg-1 group (P=0.002). Positive controls treated with CTLA4-Ig and cyclosporine had significant histological improvement, whereas plaques treated with saline and isotype controls (human and mouse IgG2) remained unchanged. In vitro studies have shown that FR255734 effectively blocked T-cell proliferation and proinflammatory cytokine production. These observations warrant studies to evaluate the efficacy of FR255734 in human autoimmune diseases.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1969-1976 |
| Number of pages | 8 |
| Journal | Journal of Investigative Dermatology |
| Volume | 128 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2008 |
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ASJC Scopus subject areas
- Dermatology
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FR255734, a humanized, Fc-silent, anti-CD28 antibody, improves psoriasis in the SCID mouse-psoriasis xenograft model. / Raychaudhuri, Siba P; Kundu-Raychaudhuri, Smriti; Tamura, Kouichi; Masunaga, Taro; Kubo, Kaori; Hanaoka, Kaori; Jiang, Wen Yue; Herzenberg, Leonore A.; Herzenberg, Leonard A.
In: Journal of Investigative Dermatology, Vol. 128, No. 8, 08.2008, p. 1969-1976.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - FR255734, a humanized, Fc-silent, anti-CD28 antibody, improves psoriasis in the SCID mouse-psoriasis xenograft model
AU - Raychaudhuri, Siba P
AU - Kundu-Raychaudhuri, Smriti
AU - Tamura, Kouichi
AU - Masunaga, Taro
AU - Kubo, Kaori
AU - Hanaoka, Kaori
AU - Jiang, Wen Yue
AU - Herzenberg, Leonore A.
AU - Herzenberg, Leonard A.
PY - 2008/8
Y1 - 2008/8
N2 - In psoriasis, CD28/B7 costimulatory molecules are well characterized. Here, using the severe combined immunodeficient (SCID) mouse-psoriasis xenograft model, we report therapeutic efficacy of a humanized anti-CD28 monoclonal antibody (FR255734; Astellas Pharmaceuticals Inc., Tokyo, Japan). Transplanted psoriasis plaques on the SCID mouse were treated weekly for 4 weeks with intraperitoneal injections of FR255734 at 10, 3, and 1-mg kg-1 doses. Groups treated with doses of 10 and 3 mg kg-1had significant thinning of the epidermis and reduced HLA-DR-positive lymphocytic infiltrates. The length of the rete pegs changed from 415.2±59.6 to 231.4±40.4 μm (P<0.005) in the 10-mg kg-1 group, and from 323.4±69.6 to 237.5±73.6 μm in the 3-mg kg-1 group (P=0.002). Positive controls treated with CTLA4-Ig and cyclosporine had significant histological improvement, whereas plaques treated with saline and isotype controls (human and mouse IgG2) remained unchanged. In vitro studies have shown that FR255734 effectively blocked T-cell proliferation and proinflammatory cytokine production. These observations warrant studies to evaluate the efficacy of FR255734 in human autoimmune diseases.
AB - In psoriasis, CD28/B7 costimulatory molecules are well characterized. Here, using the severe combined immunodeficient (SCID) mouse-psoriasis xenograft model, we report therapeutic efficacy of a humanized anti-CD28 monoclonal antibody (FR255734; Astellas Pharmaceuticals Inc., Tokyo, Japan). Transplanted psoriasis plaques on the SCID mouse were treated weekly for 4 weeks with intraperitoneal injections of FR255734 at 10, 3, and 1-mg kg-1 doses. Groups treated with doses of 10 and 3 mg kg-1had significant thinning of the epidermis and reduced HLA-DR-positive lymphocytic infiltrates. The length of the rete pegs changed from 415.2±59.6 to 231.4±40.4 μm (P<0.005) in the 10-mg kg-1 group, and from 323.4±69.6 to 237.5±73.6 μm in the 3-mg kg-1 group (P=0.002). Positive controls treated with CTLA4-Ig and cyclosporine had significant histological improvement, whereas plaques treated with saline and isotype controls (human and mouse IgG2) remained unchanged. In vitro studies have shown that FR255734 effectively blocked T-cell proliferation and proinflammatory cytokine production. These observations warrant studies to evaluate the efficacy of FR255734 in human autoimmune diseases.
UR - http://www.scopus.com/inward/record.url?scp=47349131344&partnerID=8YFLogxK
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U2 - 10.1038/jid.2008.38
DO - 10.1038/jid.2008.38
M3 - Article
VL - 128
SP - 1969
EP - 1976
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 8
ER -