US2020188366A1PendingUtilityA1

Histone deacetylase as a modulator of pdli expression and activity

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Assignee: H LEE MOFFITT CANCER CT & RESPriority: Apr 6, 2014Filed: Feb 25, 2020Published: Jun 18, 2020
Est. expiryApr 6, 2034(~7.7 yrs left)· nominal 20-yr term from priority
Inventors:Alejandro V. VillagraEduardo M. Sotomayor
A61K 31/422A61K 31/416A61K 45/06A61K 31/17A61K 31/4406A61K 31/506A61K 31/505A61K 31/437A61K 31/4045
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Claims

Abstract

Disclosed herein is a method for modulating Program Death Receptor Ligand 1 (PDL1) in a cancer cell, comprising contacting the cell with a composition comprising a histone deacetylase (HDAC) inhibitor. Also disclosed is a method for treating a tumor in a subject, comprising administering to the subject a thereapeutically effective amount of a composition comprising a histone deacetylase (HDAC) inhibitor and a composition comprising a thereapeutically effective amount of a Program Death Receptor Ligand 1 (PDL1) inhibitor, a Programmed Death 1 receptor (PD1) inhibitor, or a combination thereof.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method for modulating Program Death Receptor Ligand 1 (PDL1) in a cancer cell, comprising contacting the cell with a composition comprising a histone deacetylase (HDAC) inhibitor. 
     
     
         2 . The method  claim 1 , wherein the HDAC inhibitor comprises a selective inhibitor of histone deacetylase 6 (HDAC6). 
     
     
         3 . The method  claim 2 , wherein the HDAC6 inhibitor is selected from the group consisting of ACY-1215, Tubacin, Tubastatin A, ST-3-06, ST-2-92, Nexturastat A, and Nexturastat B. 
     
     
         4 . The method of any one of  claims 1  to  3 , wherein the HDAC inhibitor comprises a pan inhibitor, a class I HDAC inhibitor, or a combination thereof. 
     
     
         5 . A method for treating a tumor in a subject, comprising administering to the subject a thereapeutically effective amount of a histone deacetylase (HDAC) inhibitor and a thereapeutically effective amount of a Program Death Receptor Ligand 1 (PDL1) inhibitor, a Programmed Death  1  receptor (PD 1 ) inhibitor, or a combination thereof. 
     
     
         6 . The method of  claim 5 , wherein the HDAC inhibitor is a class I HDAC inhibitor. 
     
     
         7 . The method of  claim 6 , wherein the tumor comprises low PDL1 expression. 
     
     
         8 . The method of  claim 5 , wherein the HDAC inhibitor is a selective HDAC6 inhibitor. 
     
     
         9 . The method of  claim 8 , wherein the selective HDAC6 inhibitor is selected from the group consisting of ACY-1215, Tubacin, Tubastatin A, ST-3-06, ST-2-92, Nexturastat A, and Nexturastat B. 
     
     
         10 . The method of any one of  claims 5  to  9 , wherein the tumor comprises a melanoma, renal cancer, or non-small cell lung cancer. 
     
     
         11 . The method of any preceding claim, wherein the PDL1 inhibitor comprises an antibody that specifically binds PDL1. 
     
     
         12 . The method of any preceding claim, wherein the PD 1  inhibitor comprises an antibody that specifically binds PD1.

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