Pde inhibitors in 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 - 16 . (canceled) 
     
     
         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 . The method of  claim 1 , further comprising the step of assessing MSC levels in the subject before and after administration. 
     
     
         22 . The method of  claim 20  or  21 , wherein the assessment is by surface marker expression. 
     
     
         23 . The method of  claim 20  or  21 , wherein the assessment is by MSC number. 
     
     
         24 . The method of  claim 20  or  21 , wherein the assessment is by measure of immunosuppression function. 
     
     
         25 . The method of  claim 1 , wherein the cancer is multiple myeloma, lymphomas, melanoma, breast, stomach, head and neck, ovarian, colon, prostate, lung, high grade gliomas, or cervical cancer. 
     
     
         26 - 32 . (canceled)