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1356 QUADRUPLE THERAPY WITH BMS-790052, BMS-650032 AND PEG-IFN/RBV FOR 24 WEEKS RESULTS IN 100% SVR12 IN HCV GENOTYPE 1 NULL RESPONDERS

2011; Elsevier BV; Volume: 54; Linguagem: Inglês

10.1016/s0168-8278(11)61358-5

1600-0641

Anna S. Lok, David Gardiner, Eric Lawitz, Claudia Martorell, G. Everson, R. Ghalib, Robert Reindollar, V. Rustgi, Fiona McPhee, Megan Wind‐Rotolo, Anja Bondke Persson, Kuang kuang Zhu, Dessislava I. Dimitrova, Timothy Eley, Tao Guo, Dennis M. Grasela, C Pasquinelli,

Biochemical and Molecular Research

Background and Aims: The chemokine IP-10 (or CXCL10) has been identified to be a negative predictor for response to pegylated-interferon (peg-IFN)-a2/ribavirin (RBV) therapy. We have recently demonstrated that in the context of chronic HCV disease pathogenesis, IP-10 is cleaved by the enzyme dipeptidylpeptidase IV (DPP4 or CD26), converting it from an agonist into an antagonist (Casrouge et al, JCI 2011). We have now established an experimental model to evaluate the impact of DPP4 inhibition as a strategy for enhancing lymphocyte cell trafficking to the liver. Methods: We have conducted human subject studies and established small animal models to evaluate the impact of DPP4 inhibition of lymphocyte trafficking. We utilize novel assays capable of distinguishing the agonist and antagonist forms of human IP-10; clinically approved inhibitors; as well as genetic knock-out animals deficient in DPP4 to study the regulation of lymphocyte trafficking. Using patient data and infection models in mice we study T and NK cell trafficking to sites of inflammation, including the liver parenchyma.