PD-1 Modulation And Uses Thereof
For Modulating HIV Replication

PCT/CA2011/050096, Canadian Patent Application No. 2,790,134
Priority Date: February 16, 2010

Nicolas Chomont, PhD, Vaccine & Gene Therapy Institute of Florida
Rafick-Pierre Sekaly PhD, Vaccine & Gene Therapy Institute of Florida
Elias Haddad, PhD, Vaccine & Gene Therapy Institute of Florida

PD-1 (Programmed Death-1), a transmembrane protein of the Ig superfamily negatively regulates T-cell activation and effector function. When activated by its ligands it plays an important role in tumor evasion from host immunity and in immune function in chronic infections, such as HIV.  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 methods, uses, compositions, and kits for modulating HIV replication based on PD-1 modulation.  In addition, methods, uses, compositions and kits useful for the elimination of latent HIV reservoirs based on PD-1 inhibition are also disclosed.  Methods and kits for identifying agents useful for modulating HIV replication are also described.

Key Words: Programmed Death-1, PD-1, immunomodulation, T-Cell activation, HIV, AIDS

Publication: Chomont, N., M. El-Far, P. Ancuta, L. Trautmann, F. A. Procopio, B. Yassine-Diab, G. Boucher, M. R. Boulassel, G. Ghattas, J. M. Brenchley, T. W. Schacker, B. J. Hill, D. C. Douek, J. P. Routy, E. K. Haddad, and R. P. Sekaly. 2009. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med 15:893-900. PMID:19543283

Chomont, N., S. DaFonseca, C. Vandergeeten, P. Ancuta, and R. P. Sekaly. 2011. Maintenance of CD4+ T-cell memory and HIV persistence: keeping memory, keeping HIV. Curr Opin HIV AIDS 6:30-36. PMID:21242891

Trono, D., C. Van Lint, C. Rouzioux, E. Verdin, F. Barre-Sinoussi, T. W. Chun, and N. Chomont. 2010. HIV persistence and the prospect of long-term drug-free remissions for HIV-infected individuals. Science 329:174-180. PMID:20616270

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PD-1 Modulation and uses therof for Modulating HIV Replication (Non Confidential Summary 1509…)