Abstract:
INTRODUCTION:We previously demonstrated that a single-chain fragment variable (scFv) specific to collagen type II (CII) posttranslationally modified by reactive oxygen species (ROS) can be used to target anti-inflammatory therapeutics specifically to inflamed arthritic joints. The objective of the present study was to demonstrate the superior efficacy of anti-inflammatory cytokines when targeted to inflamed arthritic joints by the anti-ROS modified CII (anti-ROS-CII) scFv in a mouse model of arthritis. METHODS:Viral interleukin-10 (vIL-10) was fused to anti-ROS-CII scFv (1-11E) with a matrix-metalloproteinase (MMP) cleavable linker to create 1-11E/vIL-10 fusion. Binding of 1-11E/vIL-10 to ROS-CII was determined by enzyme-linked immunosorbent assay (ELISA), Western blotting, and immune-staining of arthritic cartilage, whereas vIL-10 bioactivity was evaluated in vitro by using an MC-9 cell-proliferation assay. Specific in vivo localization and therapeutic efficacy of 1-11E/vIL-10 was tested in the mouse model of antigen-induced arthritis. RESULTS:1-11E/vIL-10 bound specifically to ROS-CII and to damaged arthritic cartilage. Interestingly, the in vitro vIL-10 activity in the fusion protein was observed only after cleavage with MMP-1. When systemically administered to arthritic mice, 1-11E/vIL-10 localized specifically to the arthritic knee, with peak accumulation observed after 3 days. Moreover, 1-11E/vIL-10 reduced inflammation significantly quicker than vIL-10 fused to the control anti-hen egg lysozyme scFv (C7/vIL10). CONCLUSIONS:Targeted delivery of anti-inflammatory cytokines potentiates their anti-arthritic action in a mouse model of arthritis. Our results further support the hypothesis that targeting biotherapeutics to arthritic joints may be extended to include anti-inflammatory cytokines that lack efficacy when administered systemically.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Hughes C,Sette A,Seed M,D'Acquisto F,Manzo A,Vincent TL,Lim NH,Nissim Adoi
10.1186/ar4613subject
Has Abstractpub_date
2014-07-16 00:00:00pages
R151issue
4eissn
1478-6354issn
1478-6362pii
ar4613journal_volume
16pub_type
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
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doi:10.1186/ar2456
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
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doi:10.1186/s13075-017-1506-7
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abstract::Human T cell leukaemia virus type I (HTLV-I) is known to be involved in late-onset chronic polyarthritis as HTLV-I-associated arthropathy. However, it is unclear whether HTLV-I infection could modify the pathophysiology of osteoarthritis (OA). In this study we compared several inflammatory cytokines, such as C-termina...
journal_title:Arthritis research & therapy
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pub_type: 临床试验,杂志文章
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pub_type: 杂志文章,随机对照试验
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0982-5
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journal_title:Arthritis research & therapy
pub_type: 评论,社论
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更新日期:2014-05-30 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4493
更新日期:2014-02-25 00:00:00
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journal_title:Arthritis research & therapy
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更新日期:2012-04-02 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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journal_title:Arthritis research & therapy
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更新日期:2015-09-04 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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更新日期:2013-10-29 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0918-0
更新日期:2016-01-16 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4345
更新日期:2013-10-24 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4427
更新日期:2014-01-02 00:00:00
abstract:INTRODUCTION:The major histocompatibility complex (H-2d) and non-major histocompatibility complex genetic backgrounds make the BALB/c strain highly susceptible to inflammatory arthritis and spondylitis. Although different BALB/c colonies develop proteoglycan-induced arthritis and proteoglycan-induced spondylitis in res...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2613
更新日期:2009-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2018-03-23 00:00:00
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pub_type: 杂志文章
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更新日期:2010-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/ar3702
更新日期:2012-01-27 00:00:00