Tropism modified cancer terminator virus (ad.5/3 ctv;ad.5/3-ctv-m7)

Abstract

A tropism modified cancer terminator virus (Ad.5/3-CTV; Ad.5/3-CTV-M7) has been found to have infectivity that is Coxsackie Adenoviral Receptor (CAR) independent. The Ad.5/3-CTV (Ad.5/3-CTV-M7) may be used alone or in combination with other therapeutic agents such as agents that augment reactive oxygen (ROS) production, HDAC inhibitors, MCL-1 inhibitors and Bcl-2 inhibitors to treat a variety of cancers particularly including malignant glioma (GBM), renal cancer, prostate cancer, and colorectal cancer.

1 .- 17 . (canceled) 
     
     
         18 . A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition comprising an adenovirus, wherein:
 (a) the adenovirus comprises a genome encoding a melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) protein;   (b) the adenovirus comprises a fiber comprising (i) a portion of an adenovirus serotype 5 fiber and (ii) an adenovirus serotype 3 fiber knob; and   (c) the adenovirus is replication competent in cancer cells.   
     
     
         19 . The method of  claim 18 , wherein the mda-7/IL-24 protein is encoded within an E3 region of the adenovirus genome. 
     
     
         20 . The method of  claim 18 , wherein viral replication of the adenovirus is under the control of a cancer-selective promoter. 
     
     
         21 . The method of  claim 20 , wherein the cancer-selective promoter is a Progression Elevated Gene (PEG)-3 promoter. 
     
     
         22 . The method of  claim 18 , wherein said administering is performed systemically. 
     
     
         23 . The method of  claim 22 , wherein said virus is encapsulated in microbubbles in a physiologically acceptable carrier. 
     
     
         24 . The method of  claim 18 , further comprising administering to the patient at least one additional therapeutic agent. 
     
     
         25 . The method of  claim 24 , wherein said at least one additional therapeutic agent is selected from the group consisting of an agent that augments reactive oxygen species (ROS) production, an HDAC inhibitor, and an MCL-1 inhibitor. 
     
     
         26 . The method of  claim 24 , wherein the additional agent is perillyl alcohol. 
     
     
         27 . The method of  claim 24 , wherein the additional agent is sodium valproate or suberohydroxamic acid. 
     
     
         28 . The method of  claim 24 , wherein the additional agent is sabutoclax. 
     
     
         29 . The method of  claim 18 , wherein the cancer is a carcinoma. 
     
     
         30 . The method of  claim 29 , wherein the carcinoma is an adenocarcinoma. 
     
     
         31 . The method of  claim 30 , wherein the adenocarcinoma is a prostate adenocarcinoma. 
     
     
         32 . The method of  claim 30 , wherein the adenocarcinoma is a pancreatic adenocarcinoma. 
     
     
         33 . The method of  claim 18 , wherein the cancer is a glioma. 
     
     
         34 . The method of  claim 33 , wherein the glioma is a glioblastoma.