Abatacept: a costimulatory inhibitor for treatment of rheumatoid arthritis

被引:31
作者
Teng, GG [1 ]
Turkiewicz, AM [1 ]
Moreland, LW [1 ]
机构
[1] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA
关键词
abatacept; biological response modifiers; costimulatory blockade; CTLA4; immunoglobulin; rheumatoid arthritis;
D O I
10.1517/14712598.5.9.1245
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
T cell costimulation is believed to be crucial in orchestrating immune responses that lead to inflammation and destruction in rheumatoid arthritis (RA). Abatacept is a novel recombinant CTLA41g fusion protein that selectively modulates costimulation via interrupting the CD28:CD80/86 pathway, resulting in clownregulation of T cell activation and multiple ensuing effector mechanisms. Abatacept has been shown to be efficacious, either when given alone or in combination with methotrexate, in patients with active RA, including anti-TNF failures. Improvements in clinical signs and symptoms, slowing of radiological progression, and enhancement in patient function and pain have been reported in clinical trials. infusions were well-tolerated with a favourable safety profile similar to placebo and no appreciable immunogenicity. Abatacept is the first in a new class of biological response modifiers called costimulatory blockers.
引用
收藏
页码:1245 / 1254
页数:10
相关论文
共 62 条
[1]   CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris [J].
Abrams, JR ;
Lebwohl, MG ;
Guzzo, CA ;
Jegasothy, BV ;
Goldfarb, MT ;
Goffe, BS ;
Menter, A ;
Lowe, NJ ;
Krueger, G ;
Brown, MJ ;
Weiner, RS ;
Birkhofer, MJ ;
Warner, GL ;
Berry, KK ;
Linsley, PS ;
Krueger, JG ;
Ochs, HD ;
Kelley, SL ;
Kang, SW .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (09) :1243-1252
[2]   Blockade of T lymphocyte costimulation with cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4Ig) reverses the cellular pathology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells [J].
Abrams, JR ;
Kelley, SL ;
Hayes, E ;
Kikuchi, T ;
Brown, MJ ;
Kang, SW ;
Lebwohl, MG ;
Guzzo, CA ;
Jegasothy, BV ;
Linsley, PS ;
Krueger, JG .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (05) :681-693
[3]   CTLA4IG PROLONGS ALLOGRAFT SURVIVAL WHILE SUPPRESSING CELL-MEDIATED-IMMUNITY [J].
BALIGA, P ;
CHAVIN, KD ;
QIN, LH ;
WOODWARD, J ;
LIN, JX ;
LINSLEY, PS ;
BROMBERG, JS .
TRANSPLANTATION, 1994, 58 (10) :1082-1090
[4]  
Bresnihan B, 1998, ARTHRITIS RHEUM, V41, P2196, DOI 10.1002/1529-0131(199812)41:12<2196::AID-ART15>3.0.CO
[5]  
2-2
[6]  
Brunner MC, 1999, J IMMUNOL, V162, P5813
[7]   Multiple functions for CD28 and cytotoxic T lymphocyte antigen-4 during different phases of T cell responses: implications for arthritis and autoimmune diseases [J].
Brunner-Weinzierl, MC ;
Hoff, H ;
Burmester, GR .
ARTHRITIS RESEARCH & THERAPY, 2004, 6 (02) :45-54
[8]   Mechanisms of disease: Cytokine pathways and joint inflammation in rheumatoid arthritis. [J].
Choy, EHS ;
Panayi, GS .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (12) :907-916
[9]   Combination of infliximab and methotrexate therapy for early rheumatoid arthritis - A randomized, controlled trial [J].
Clair, EWS ;
van der Heijde, DMFM ;
Smolen, JS ;
Maini, RN ;
Bathon, JM ;
Emery, P ;
Keystone, E ;
Schiff, M ;
Kalden, JR ;
Wang, B ;
DeWoody, K ;
Weiss, R ;
Baker, D .
ARTHRITIS AND RHEUMATISM, 2004, 50 (11) :3432-3443
[10]   LONG-TERM INHIBITION OF MURINE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS USING CTLA-4-FC SUPPORTS A KEY ROLE FOR CD28 COSTIMULATION [J].
CROSS, AH ;
GIRARD, TJ ;
GIACOLETTO, KS ;
EVANS, RJ ;
KEELING, RM ;
LIN, RF ;
TROTTER, JL ;
KARR, RW .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (06) :2783-2789