FR255734, a humanized, Fc-silent, anti-CD28 antibody, improves psoriasis in the SCID mouse-psoriasis xenograft model

Siba P Raychaudhuri, Smriti Kundu-Raychaudhuri, Kouichi Tamura, Taro Masunaga, Kaori Kubo, Kaori Hanaoka, Wen Yue Jiang, Leonore A. Herzenberg, Leonard A. Herzenberg

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1969-1976
Number of pages8
JournalJournal of Investigative Dermatology
Volume128
Issue number8
DOIs
StatePublished - Aug 2008

Fingerprint

SCID Mice
Psoriasis
Heterografts
Anti-Idiotypic Antibodies
Antibodies
B7 Antigens
T-cells
Tokyo
Cell proliferation
HLA-DR Antigens
Intraperitoneal Injections
Epidermis
Cyclosporine
Autoimmune Diseases
Japan
Immunoglobulin G
Cell Proliferation
Cytokines
T-Lymphocytes
FR255734 monoclonal antibody

ASJC Scopus subject areas

  • Dermatology

Cite this

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 journalArticle

Raychaudhuri, SP, Kundu-Raychaudhuri, S, Tamura, K, Masunaga, T, Kubo, K, Hanaoka, K, Jiang, WY, Herzenberg, LA & Herzenberg, LA 2008, 'FR255734, a humanized, Fc-silent, anti-CD28 antibody, improves psoriasis in the SCID mouse-psoriasis xenograft model', Journal of Investigative Dermatology, vol. 128, no. 8, pp. 1969-1976. https://doi.org/10.1038/jid.2008.38
Raychaudhuri, Siba P ; Kundu-Raychaudhuri, Smriti ; Tamura, Kouichi ; Masunaga, Taro ; Kubo, Kaori ; Hanaoka, Kaori ; Jiang, Wen Yue ; Herzenberg, Leonore A. ; Herzenberg, Leonard A. / FR255734, a humanized, Fc-silent, anti-CD28 antibody, improves psoriasis in the SCID mouse-psoriasis xenograft model. In: Journal of Investigative Dermatology. 2008 ; Vol. 128, No. 8. pp. 1969-1976.
@article{82af1d39d0a74ccdaa8ce1162b6bfe68,
title = "FR255734, a humanized, Fc-silent, anti-CD28 antibody, improves psoriasis in the SCID mouse-psoriasis xenograft model",
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.",
author = "Raychaudhuri, {Siba P} and Smriti Kundu-Raychaudhuri and Kouichi Tamura and Taro Masunaga and Kaori Kubo and Kaori Hanaoka and Jiang, {Wen Yue} and Herzenberg, {Leonore A.} and Herzenberg, {Leonard A.}",
year = "2008",
month = "8",
doi = "10.1038/jid.2008.38",
language = "English (US)",
volume = "128",
pages = "1969--1976",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "8",

}

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

UR - http://www.scopus.com/inward/citedby.url?scp=47349131344&partnerID=8YFLogxK

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 -