Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 610, Issue 1-3, Pages 110-118Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2009.03.023
Keywords
B7RP-1; ICOS; Humoral immune response; Keyhole limpet hemocyanin (KLH); Costimulation; Target occupancy assay; 1B7v2
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The ICOS (Inducible T cell Co-Stimulator)/B7RP-1 (B7-related protein 1) interaction is critical for the proper activation of a T lymphocyte. In this manuscript we describe a systematic in vivo approach to determine the level of blockade required to impair the generation of a T cell-dependent antibody response. We have developed an overall strategy for correlating drug exposure, target saturation, and efficacy in a biological response that can be generalized for most protein therapeutics. Using this strategy, we determined that low levels of B7RP-1 blockade are still sufficient to inhibit the immune response. These data suggest that contact between the T cell and the antigen-presenting cell during antigen presentation is much more sensitive to inhibition than previously believed and that ICOS/B7RP-1 blockade may be efficacious in the treatment of autoimmune diseases. (C) 2009 Elsevier B.V. All rights reserved.
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