PSGL-1 Antagonists and Uses Thereof

Abstract

Methods of identifying and using PSGL-1 antagonists are provided. Such methods include, but are not limited to, methods of treating cancer. PSGL-1 antagonists include, but are not limited to, antibodies that bind PSGL-1 and antibodies that bind VISTA, wherein the antibodies inhibit PSGL-1 binding to VISTA, e.g., at acidic pH (e.g., pH 6.0), as well as PSGL-1 and VISTA extracellular domain polypeptides.

1 . A method of treating cancer and/or of inhibiting binding of PSGL-1 to VISTA in a subject, comprising administering to the subject an effective amount of at least one PSGL-1 antagonist. 
     
     
         2 . The method of  claim 1 , wherein the method further comprises administering to the subject an effective amount of a therapeutic agent selected from chemotherapeutic agents, anti-angiogenesis agents, growth inhibitory agents, immune-oncology agents, and anti-neoplastic compositions. 
     
     
         3 . The method of  claim 1 , wherein the PSGL-1 antagonist is selected from a PSGL-1 antibody and a VISTA antibody. 
     
     
         4 .- 5 . (canceled) 
     
     
         6 . The method of  claim 3 , wherein the antibody is selected from a chimeric antibody, a humanized antibody, a human antibody, and an antibody fragment selected from an Fv, a single-chain Fv (scFv), a Fab, a Fab′, and a (Fab′) 2 . 
     
     
         7 .- 8 . (canceled) 
     
     
         9 . The method of  claim 3 , wherein the PSGL-1 antagonist is an antibody that blocks binding of PSGL-1 to VISTA, at a pH in the range of pH 5.5 to pH 6.5. 
     
     
         10 . The method of  claim 3 , wherein the PSGL-1 antagonist is an antibody that binds to VISTA at a pH in the range of pH 5.5 to pH 6.5 or an antibody that binds to PSGL 1 at a pH in the range of pH 5.5 to pH 6.5. 
     
     
         11 . The method of  claim 3 , wherein the antibody binds to VISTA or PSGL-1 with a K D  of 10 nM or less. 
     
     
         12 .- 38 . (canceled) 
     
     
         39 . A method of inhibiting binding of PSGL-1 to VISTA on a cell comprising contacting the cell with at least one PSGL-1 antagonist. 
     
     
         40 . The method of  claim 39 , wherein the cell is in vitro. 
     
     
         41 . The method of  claim 39 , wherein the PSGL-1 antagonist is selected from a PSGL-1 antibody and a VISTA antibody. 
     
     
         42 .- 43 . (canceled) 
     
     
         44 . The method of  claim 41 , wherein the antibody is selected from a chimeric antibody, a humanized antibody, a human antibody, and an antibody fragment selected from an Fv, a single-chain Fv (scFv), a Fab, a Fab′, and a (Fab′) 2 . 
     
     
         45 .- 46 . (canceled) 
     
     
         47 . The method of  claim 41 , wherein the PSGL-1 antagonist is an antibody that blocks binding of PSGL-1 to VISTA at a pH in the range of pH 5.5 to pH 6.5. 
     
     
         48 . The method of  claim 41 , wherein the PSGL-1 antagonist is an antibody that binds to VISTA at a pH in the range of pH 5.5 to pH 6.5 or an antibody that binds to PSGL-1 at a pH in the range of pH 5.5 to pH 6.5. 
     
     
         49 . The method of  claim 41 , wherein the antibody binds to VISTA or PSGL-1 with a K D  of 10 nM or less. 
     
     
         50 .- 65 . (canceled) 
     
     
         66 . A PSGL-1 antagonist, which inhibits at least partially the binding of VISTA to PSGL-1, at a pH in the range of pH 5.5 to pH 6.5. 
     
     
         67 . The PSGL-1 antagonist of  claim 66 , which inhibits by at least 90% the binding of VISTA to PSGL-1, at a pH in the range of pH 5.5 to pH 6.5. 
     
     
         68 .- 69 . (canceled) 
     
     
         70 . The PSGL-1 antagonist of  claim 66 , wherein the antagonist is selected from a PSGL-1 antibody and a VISTA antibody. 
     
     
         71 .- 72 . (canceled) 
     
     
         73 . The PSGL-1 antagonist of  claim 70 , wherein the antibody is selected from a chimeric antibody, a humanized antibody, a human antibody, and an antibody fragment selected from an Fv, a single-chain Fv (scFv), a Fab, a Fab′, and a (Fab′) 2 . 
     
     
         74 .- 75 . (canceled) 
     
     
         76 . A composition comprising a PSGL-1 antagonist of  claim 66 . 
     
     
         77 .- 78 . (canceled)