RGD Reference Report - ARG098, a novel anti-human Fas antibody, suppresses synovial hyperplasia and prevents cartilage destruction in a severe combined immunodeficient-HuRAg mouse model.

General

ARG098, a novel anti-human Fas antibody, suppresses synovial hyperplasia and prevents cartilage destruction in a severe combined immunodeficient-HuRAg mouse model.
Authors:	Odani-Kawabata, Noriko Takai-Imamura, Miwa Katsuta, Osamu Nakamura, Hiroshi Nishioka, Kusuki Funahashi, Keiko Matsubara, Tsukasa Sasano, Minoru Aono, Hiroyuki
Citation:	Odani-Kawabata N, etal., BMC Musculoskelet Disord. 2010 Sep 27;11:221. doi: 10.1186/1471-2474-11-221.
RGD ID:	12903969
Pubmed:	PMID:20875116 (View Abstract at PubMed)
PMCID:	PMC3161399 (View Article at PubMed Central)
DOI:	DOI:10.1186/1471-2474-11-221 (Journal Full-text)
BACKGROUND: The anti-human Fas/APO-1/CD95 (Fas) mouse/human chimeric monoclonal IgM antibody ARG098 (ARG098) targets the human Fas molecule. The cytotoxic effects of ARG098 on cells isolated from RA patients, on normal cells in vitro, and on RA synovial tissue and cartilage in vivo using implanted rheumatoid tissues in an SCID mouse model (SCID-HuRAg) were investigated to examine the potential of ARG098 as a therapy for RA. METHODS: ARG098 binding to each cell was analyzed by cytometry. The effects of ARG098 on several cells were assessed by a cell viability assay in vitro. Effects on the RA synovium, lymphocytes, and cartilage were assessed in vivo using the SCID-HuRAg mouse model. RESULTS: ARG098 bound to cell surface Fas molecules, and induced apoptosis in Fas-expressing RA synoviocytes and infiltrating lymphocytes in the RA synovium in a dose-dependent manner. However, ARG098 did not affect the cell viability of peripheral blood mononuclear cells of RA patients or normal chondrocytes. ARG098 also induced apoptosis in RA synoviocytes and infiltrating lymphocytes in the RA synovium in vivo. The destruction of cartilage due to synovial invasion was inhibited by ARG098 injection in the modified SCID-HuRAg mouse model. CONCLUSIONS: ARG098 treatment suppressed RA synovial hyperplasia through the induction of apoptosis and prevented cartilage destruction in vivo. These results suggest that ARG098 might become a new therapy for RA.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
rheumatoid arthritis		IMP		12903969		RGD
rheumatoid arthritis		ISO	FAS (Homo sapiens)	12903969; 12903969		RGD

Objects Annotated

Genes (Rattus norvegicus)

Fas (Fas cell surface death receptor)

Genes (Mus musculus)

Fas (Fas cell surface death receptor)

Genes (Homo sapiens)

FAS (Fas cell surface death receptor)

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ARG098, a novel anti-human Fas antibody, suppresses synovial hyperplasia and prevents cartilage destruction in a severe combined immunodeficient-HuRAg mouse model.