Engineered Dendritic Cells and Uses for the Treatment of Cancer

Abstract

This invention provides the field of therapeutics. Most specifically present invention provides methods of generating in vitro engineered dendritic cells conditionally expressing interleukin-12 (IL-12) under the control of a gene expression modulation system in the presence of activating ligand and uses for therapeutic purposes in animals including human.

1 - 38 . (canceled) 
     
     
         39 . A method for determining the efficacy of an in vitro engineered dendritic cell based therapeutic regime in a patient comprising:
 (a) measuring the level of expression or the level of activity or both of interferon-gamma (IFN-γ) in a first biological sample obtained from said patient in need thereof before administration of in vitro engineered dendritic cells, thereby generating a control level;   (b) administering to a patient in need thereof, the in vitro engineered dendritic cell of claim  18  or  19 ;   (c) administering to said patient in need thereof an effective amount of an activating ligand;   (d) measuring the level of expression or the level of activity or both of IFN-γ in a second biological sample obtained from said patient in need thereof following administration of in vitro engineered DC and activating ligand, thereby generating a test level; and   (e) comparing the control level to the test level of IFN-γ, wherein an increase in the test level of expression, activity or both of IFN-γ relative to the control level indicates that the therapeutic regime is effective in said patient in need thereof.   
     
     
         40 . The method of  claim 39 , wherein said patient in need thereof is a human patient. 
     
     
         41 . The method of  claim 39 , wherein said patient is a cancer patient. 
     
     
         42 . The method of  claim 41 , wherein said cancer patient is a melanoma patient. 
     
     
         43 . The method of  claim 39 , wherein the level of IFN-γ is measured by ELISA. 
     
     
         44 . The method of any one of  claims 39 - 43 , wherein said ligand is a diacylhydrazine. 
     
     
         45 . The method of  claim 44 , wherein said ligand is selected from the group consisting of RG-115819, RG-115932, and RG-115830. 
     
     
         46 . The method of  claim 39 , wherein said ligand is an amidoketone or oxadiazoline. 
     
     
         47 . The method of any one of  claims 39 - 46 , wherein said ligand is administered intratumorally, orally, intraperitoneally, or subcutaneously. 
     
     
         48 . The method of any one of  claims 39 - 47 , wherein said ligand is administered less than one hour before or after said in vitro engineered dendritic cell. 
     
     
         49 . The method of any one of  claims 39 - 47 , wherein said ligand is administered within less than 24 hours after said in vitro engineered dendritic cell. 
     
     
         50 . The method of any one of  claims 39 - 47 , wherein said ligand is administered within less than 48 hours after said in vitro engineered dendritic cell. 
     
     
         51 - 73 . (canceled)