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T cell immunomodulation-the Holy Grail of therapeutic tolerance

Lookup NU author(s): Professor John Isaacs

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Abstract

The concept and practice of therapeutic tolerance has successfully been applied to animal models of autoimmunity and transplantation for more than 2 decades. Finally, there are encouraging signs of its translation to clinical practice. Short courses of anti-CD3 monoclonal antibody therapy have provided lasting benefits in recent-onset type 1 diabetes in association with evidence for the induction of immunoregulatory mechanisms. Co-stimulation blockade with abatacept (CTLA4-Ig) will soon be licensed for the treatment of rheumatoid arthritis - over the past year phase III studies have demonstrated impressive improvement in subjective and objective signs of the disease. T cell depletion is in development for several conditions, again with recent studies demonstrating evidence of immune regulation in some instances. More specific antigen-directed peptide therapies have also been applied to atopic asthma, type 1 diabetes, and adult and juvenile arthritis. The tragic sequelae of the phase I trial of TGN1412 at Northwick Park demonstrated the delicate, but unpredictable, therapeutic ratio of some T-cell-directed treatments and, in the UK, have led to new guidelines for early-phase clinical trials of immune-directed therapies. © 2007 Elsevier Ltd. All rights reserved.


Publication metadata

Author(s): Isaacs JD

Publication type: Article

Publication status: Published

Journal: Current Opinion in Pharmacology

Year: 2007

Volume: 7

Issue: 4

Pages: 418-425

ISSN (print): 1471-4892

ISSN (electronic): 1471-4973

Publisher: Elsevier Ltd.

URL: http://dx.doi.org/10.1016/j.coph.2007.05.001

DOI: 10.1016/j.coph.2007.05.001

PubMed id: 17611158


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