Therapeutic compositions and methods of use for treating cancer

Abstract

The present invention relates to compositions and methods for treating cancer. More specifically, the present invention relates to compositions of engineered oncolytic viruses for administration to a subject with cancer that specifically lyse tumor cells and actively target tumor cells and cell debris to antigen presenting cells, in order to generate anti-tumor immunity.

1 . An oncolytic virus comprising a nucleic acid encoding a hexosyl transferase enzyme. 
     
     
         2 . The oncolytic virus according to  claim 1 , wherein the enzyme is a galactosyltransferase enzyme. 
     
     
         3 . The oncolytic virus according to  claim 1 , wherein the enzyme is an alpha 1,3-galactosyltransferase enzyme. 
     
     
         4 . The oncolytic virus according to  claim 1 , which comprises a recombinant binding domain specific for a tumor stem cell marker. 
     
     
         5 . The oncolytic virus according to  claim 1 , which is replication restricted. 
     
     
         6 . The oncolytic virus according to  claim 1 , which is an RNA or DNA based virus of human or non-human origin. 
     
     
         7 . The oncolytic virus according to  claim 6 , which is an adenovirus. 
     
     
         8 . The oncolytic virus according to  claim 7 , which is a conditionally replicating adenovirus (CRAd). 
     
     
         9 . The oncolytic virus according to  claim 8 , which is an Ad5/3 chimeric virus. 
     
     
         10 . The oncolytic virus according to  claim 9 , wherein the Ad5/3 chimeric virus additionally comprises a 24-base pair deletion (Δ24) in constant region 2 (CR2) of the viral immediately early (E1a) gene (Ad5/3-Δ24 CRAd). 
     
     
         11 . The oncolytic virus according to  claim 1 , which comprises a nucleic acid sequence encoding alpha 1,3-galactosyl transferase. 
     
     
         12 . The oncolytic virus according to  claim 11 , which is an Ad5/3-Δ24-αGT CRAd (CRAd-αGT). 
     
     
         13 . A pharmaceutical composition comprising the oncolytic virus according to  claim 1 , in combination with a pharmaceutically acceptable carrier. 
     
     
         14 . The pharmaceutical composition according to  claim 13 , which is formulated for intravenous, intramuscular, intraperitoneal, intratumoral, subcutaneous, oral, rectal, intravaginal, intranasal, transmucosal or transdermal administration. 
     
     
         15 . A method of treating an individual with a neoplasm which comprises the steps of
 i) expressing an endogenous enzyme delivered by the oncolytic virus according to  claim 1  in at least one cancer cell to modify cell membrane glycosylation; and   ii) inducing lysis of the at least one cancer cell resulting from administration of the oncolytic virus.   
     
     
         16 . The method according to  claim 15 , wherein the oncolytic virus is administered in an effective amount to infect at least one cancer cell in the individual. 
     
     
         17 . The method according to  claim 15 , which is directed to treating an individual with cancer or an individual with a tumor. 
     
     
         18 . A method of treating cancer comprising administering a therapeutically effective amount of the oncolytic virus according to  claim 1  to a patient suffering from cancer or having a neoplasm or tumor in need of treatment. 
     
     
         19 . (canceled) 
     
     
         20 . The method according to  claim 15 , wherein the cancer is selected from leukemia (e.g. myeloblastic, promyelocytic, myelomonocytic, monocytic, erythroleukemia, chronic myelocytic (granulocytic) leukemia, and chronic lymphocytic leukemia), lymphoma (e.g. Hodgkin's disease and non-Hodgkin's disease), fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, angiosarcoma, endotheliosarcoma, Ewing's tumor, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, renal cell carcinoma, hepatoma, Wilms' tumor, cervical cancer, uterine cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, oligodendroglioma, melanoma, neuroblastoma, retinoblastoma, dysplasia and hyperplasia. 
     
     
         21 . A method of preparing the oncolytic virus according to  claim 1  which comprises the step of incorporating a nucleic acid encoding a hexosyl transferase enzyme into the genome of said oncolytic virus. 
     
     
         22 . The method according to  claim 21 , wherein said incorporating step comprises cloning. 
     
     
         23 . The oncolytic virus according to  claim 6 , wherein the oncolytic virus is selected from the group consisting of adenovirus, herpesvirus, vaccinia virus, measles virus, Newcastle Disease Virus, autonomous parvoviruses, vesicular stomatitis virus (VSV) and reovirus.