Pde5 inhibitor compositions and methods for immunotherapy

Abstract

The invention features methods and compositions featuring a PDE5 inhibitor for treating or preventing immunological-mediated disease in a subject.

1 . A method of treating or preventing cancer in a subject comprising administration to the subject of a PDE-5 inhibitor compound. 
   
   
       2 . The method of  claim 1 , further comprising administration to the subject of an additional anticancer agent. 
   
   
       3 . The method of  claim 2 , wherein the additional anticancer agent is an immunotherapeutic agent. 
   
   
       4 . The method of  claim 3 , wherein the additional anticancer agent is a vaccine. 
   
   
       5 . The method of  claim 1 , wherein the subject is identified as in need of treatment of cancer with a PDE-5 inhibitor compound. 
   
   
       6 . The method of  claim 1 , wherein the PDE-5 inhibitor compound is selected from sildenafil, vardenafil or tadalafil. 
   
   
       7 . A method of modulating myeloid suppressor cells (MSCs) immune suppression in a subject comprising administration to the subject of a PDE-5 inhibitor compound. 
   
   
       8 . The method of  claim 7 , wherein the modulating is down-modulation. 
   
   
       9 . A method of modulating arginase-1 activity in a subject identified as in need of such treatment comprising administration to the subject of a PDE-5 inhibitor compound. 
   
   
       10 . The method of  claim 9 , wherein the modulating is down-regulation. 
   
   
       11 . A method of modulating nitric oxide synthase 2 (NOS2) activity in a subject identified as in need of such treatment comprising administration to the subject of a PDE-5 inhibitor compound. 
   
   
       12 . The method of  claim 11 , wherein the modulating is down-regulation. 
   
   
       13 . A method of modulating interleukin-4Rα (IL-4Rα) activity in a subject identified as in need of such treatment comprising administration to the subject of a PDE-5 inhibitor compound. 
   
   
       14 . A method of modulating CD8+ T cells in a subject identified as in need of such treatment comprising administration to the subject of a PDE-5 inhibitor compound. 
   
   
       15 . A method of improving the efficacy of immune-based treatment protocols of malignancies in a subject comprising the step of further administration to the subject of a PDE-5 inhibitor compound in addition to the immune-based treatment steps. 
   
   
       16 . The method of  claim 15 , wherein the immune-based treatment protocol is administration of a vaccine. 
   
   
       17 . A method of treating or preventing disease in a subject comprising administration to the subject of a PDE-5 inhibitor compound. 
   
   
       18 . The method of  claim 17 , wherein the disease is a disease mediated by myeloid suppressor cells (MSCs). 
   
   
       19 . The method of  claim 18 , wherein the disease is cancer, chronic infection, chronic inflammation, hematopoietic reconstitution following chemotherapy. 
   
   
       20 . The method of  claim 1 , further comprising the step of assessing MSC levels in the subject. 
   
   
       21 - 32 . (canceled)