Determining Whether A Test Compound Modulates
PD-1 Activity In Activated Immune Cells Using
Gene Expression Profiles

U.S. Patent No. 8,647,822 issued February 11, 2014
Canadian Patent Application No. 2,742,926
Priority Date: November 28, 2007

Rafick-Pierre Sekaly PhD, Vaccine & Gene Therapy Institute of Florida
Elias Haddad, PhD, Vaccine & Gene Therapy Institute of Florida
Bruce Walker, MD, Mass General Hospital
Quentin Eichbaum, MD, Massachusetts General Hospital

PD-1 (Programmed Death-1), a transmembrane protein of the Ig superfamily negatively regulates T-cell activation and effector functions. When activated by its ligands it plays an important role in tumor evasion from host immunity and in immune function in chronic infections.  This PD-1 immune checkpoint component is a well-studied drugable target because when it is blocked, the inhibitory “brakes” on immune function are released and immune function is restored. This invention discloses the utility of at least two gene expression profiles to evaluate the modulation of PD-1 activity in the presence or absence of an agent.  Reagents, kits, methods and uses thereof for modulation of immune function for the identification of modulators of PD-1 activity are described.

Key Words: Programmed Death-1, PD-1, immunomodulation, T-Cell activation, gene expression profiles

Publication: Trautmann, L, Janbazian, L, Chomont, N, Said, E, Gimmig, S, Bessette, B, Boulassel, M, Delwart, M, Sepulveda, H, Balderas, R, Routy, J.P., Elias K. Haddad and Sekaly, R.P. 2006. Upregulation of PD-1 expression in HIV specific CD8 T cells leads to reversible immune dysfunction. Nature Medicine: 12(10):1198-1202.

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Determining Wheather a Test Compond Modulates PD-1 Activity Iin Activited Immune Cell using Gene Expression Profiles (Non Confidential Summary 1508…)