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Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade
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Published on: March 14, 2011

Defining dose-response relationships in the therapeutic blockade of B7RP-1-dependent immune responses

Daniela P Metz1, Deanna Mohn, Ming Zhang

  • 1Department of Inflammation Research, Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320, USA. dmetz@amgen.com

European Journal of Pharmacology
|March 19, 2009
PubMed

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.

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