Literature DB >> 19779889

[Atacicept: a new B lymphocyte-targeted therapy for multiple sclerosis].

H-P Hartung1.   

Abstract

Multiple sclerosis (MS) has traditionally been considered to be a T cell-mediated disease. However, there is an increasing body of evidence for the involvement of B cells and autoantibodies in the pathology of this disease, providing a rationale for treatment strategies directed against B cells. This paper summarizes the evidence for a key role of B cells in the immunopathology of MS and reviews data supporting the use of a novel B cell-targeted therapy, atacicept, for this condition. Atacicept is a human recombinant fusion protein that comprises the binding portion of a receptor for both BLyS (B Lymphocyte Stimulator) and APRIL (A PRoliferation-Inducing Ligand), two cytokines that have been identified as important regulators of B cell maturation, function and survival. Atacicept has shown selective effects on cells of the B cell lineage, acting on mature B cells and blocking plasma cells and late stages of B cell development while sparing B cell progenitors and memory cells. The efficacy of atacicept in animal models of autoimmune disease and the biological activity of atacicept in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) has been demonstrated. Ongoing clinical studies are investigating the safety, tolerability and efficacy of atacicept in patients with MS, SLE and RA.

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Year:  2009        PMID: 19779889     DOI: 10.1007/s00115-009-2838-6

Source DB:  PubMed          Journal:  Nervenarzt        ISSN: 0028-2804            Impact factor:   1.214


  81 in total

Review 1.  The role of CD4+ T-cells in the development of MS.

Authors:  Sylvia Delgado; William A Sheremata
Journal:  Neurol Res       Date:  2006-04       Impact factor: 2.448

Review 2.  Toward the development of rational therapies in multiple sclerosis: what is on the horizon?

Authors:  Bernhard Hemmer; Hans-Peter Hartung
Journal:  Ann Neurol       Date:  2007-10       Impact factor: 10.422

Review 3.  The role of BAFF in immune function and implications for autoimmunity.

Authors:  Susan L Kalled
Journal:  Immunol Rev       Date:  2005-04       Impact factor: 12.988

4.  BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases.

Authors:  Viktor Roschke; Svetlana Sosnovtseva; Christopher D Ward; June S Hong; Rodger Smith; Vivian Albert; William Stohl; Kevin P Baker; Stephen Ullrich; Bernardetta Nardelli; David M Hilbert; Thi-Sau Migone
Journal:  J Immunol       Date:  2002-10-15       Impact factor: 5.422

5.  APRIL-deficient mice have normal immune system development.

Authors:  Eugene Varfolomeev; Frank Kischkel; Flavius Martin; Dhaya Seshasayee; Hua Wang; David Lawrence; Christine Olsson; Lucrece Tom; Sharon Erickson; Dorothy French; Peter Schow; Iqbal S Grewal; Avi Ashkenazi
Journal:  Mol Cell Biol       Date:  2004-02       Impact factor: 4.272

Review 6.  Rituximab-induced B cell depletion in autoimmune diseases: potential effects on T cells.

Authors:  Stamatis-Nick C Liossis; Petros P Sfikakis
Journal:  Clin Immunol       Date:  2008-03-11       Impact factor: 3.969

Review 7.  Rationale for cytotoxic monoclonal antibodies in MS.

Authors:  B S Simpson; A J Coles
Journal:  Int MS J       Date:  2007-06

8.  First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial.

Authors:  Anton Hagenbeek; Ole Gadeberg; Peter Johnson; Lars Møller Pedersen; Jan Walewski; Andrzej Hellmann; Brian K Link; Tadeusz Robak; Marek Wojtukiewicz; Michael Pfreundschuh; Michael Kneba; Andreas Engert; Pieter Sonneveld; Mimi Flensburg; Jørgen Petersen; Nedjad Losic; John Radford
Journal:  Blood       Date:  2008-04-04       Impact factor: 22.113

9.  BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth.

Authors:  P Schneider; F MacKay; V Steiner; K Hofmann; J L Bodmer; N Holler; C Ambrose; P Lawton; S Bixler; H Acha-Orbea; D Valmori; P Romero; C Werner-Favre; R H Zubler; J L Browning; J Tschopp
Journal:  J Exp Med       Date:  1999-06-07       Impact factor: 14.307

10.  Alemtuzumab vs. interferon beta-1a in early multiple sclerosis.

Authors:  Alasdair J Coles; D Alastair S Compston; Krzysztof W Selmaj; Stephen L Lake; Susan Moran; David H Margolin; Kim Norris; P K Tandon
Journal:  N Engl J Med       Date:  2008-10-23       Impact factor: 91.245

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  2 in total

Review 1.  Monoclonal antibodies and recombinant immunoglobulins for the treatment of multiple sclerosis.

Authors:  Henrik Gensicke; David Leppert; Özgür Yaldizli; Raija L P Lindberg; Matthias Mehling; Ludwig Kappos; Jens Kuhle
Journal:  CNS Drugs       Date:  2012-01-01       Impact factor: 5.749

Review 2.  Drugs in development for relapsing multiple sclerosis.

Authors:  Rehiana Ali; Richard St John Nicholas; Paolo Antonio Muraro
Journal:  Drugs       Date:  2013-05       Impact factor: 11.431

  2 in total

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