Timothy Wyant

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OBJECTIVE CCR2 is a chemokine receptor expressed by monocytes, macrophages, and a subset of T cells. Its ligand, CCL2 (monocyte chemotactic protein 1), is abundantly present in the synovium of patients with rheumatoid arthritis (RA). Blocking CCR2 prevents CCL2-mediated chemotaxis in vitro and modulates arthritis in animal models of RA. In this study we(More)
Pharmacodynamic assays are important aspects for understanding molecularly targeted anticancer agents to investigate the relationship between drug concentration (pharmacokinetics) and drug "effect" or biological activity. As new drug entities are developed that affect DNA cell cycle, a pharmacodynamic assay which measures cell cycle perturbation would be a(More)
Vedolizumab (VDZ) is a humanized monoclonal antibody in development for the treatment of inflammatory bowel disease. VDZ binds to the α4β7 integrin complex and inhibits its binding to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), thus preventing lymphocyte extravasation to gut mucosal tissues. To understand whether VDZ has additional effects that(More)
Pharmacodynamic assays are important in clinical trial design to investigate the relationship between drug concentration (pharmacokinetics) and drug "effect' or biological activity. Increasingly flow cytometry is being used to examine the pharmacodynamic effect of new drug entities. However, to date, the analytical validation of cytometry based assays is(More)
Increasingly, commercial immunoassay kits are used to support drug discovery and development. Longitudinally consistent kit performance is crucial, but the degree to which kits and reagents are characterized by manufacturers is not standardized, nor are the approaches by users to adapt them and evaluate their performance through validation prior to use.(More)
BACKGROUND AND OBJECTIVES Vedolizumab, a humanized monoclonal antibody against the α4β7 integrin, is indicated for treatment of moderately to severely active ulcerative colitis or Crohn's disease. In this placebo-controlled, double-blind, randomized, single ascending-dose study, the pharmacokinetics, pharmacodynamics, safety, and tolerability of vedolizumab(More)
Receptor occupancy measurements demonstrate the binding of a biotherapeutic agent to its extra-cellular target and represent an integral component of the pharmacodynamic (PD) portfolio utilized to advance the development and commercialization of a therapeutic agent. Coupled with traditional pharmacokinetic (PK) assessments derived from serum drug(More)
4005. P299<lb>Phosphopeptides as novel tumor antigens in colorectal cancer<lb>Sarah A Penny, Jennifer G Abelin, Abu Z Saeed, Stacy A Malaker,<lb>Paisley T Myers, Jeffrey Shabanowitz, Stephen T Ward, Donald F<lb>Hunt, Mark Cobbold<lb>University of Birmingham, Birmingham, England, UK; University of<lb>Virginia, Charlottesville, VA, USA; Stanford University,(More)
In 1994, Mississippi and Minnesota independently filed lawsuits against the tobacco industry seeking reimbursement of smoking-attributable Medicaid expenditures. Numerous other states filed similar suits over the next several years. During 1997-1998 the original pair, plus Florida and Texas, settled their suits during or on the eve of trial. In November(More)
Numbers of biotherapeutic products in development have increased over past decade. Despite providing significant benefits to patients with unmet needs, almost all protein-based biotherapeutics could induce unwanted immunogenicity, which result in a loss of efficacy and/or increase the risk of adverse reactions, such as infusion reactions, anaphylaxis, and(More)