Tropic cell based virotherapy for the treatment of cancer

Abstract

In some embodiments, methods of killing tumor cells are provided. The methods may include contacting the tumor cell with a tropic cell that carries a modified oncolytic virus, wherein the virus comprises a tumor selective element and/or a capsid protein that binds a tumor-specific cell surface molecule. In another embodiment, methods of treating cancer are provided. The methods may include administering a therapeutically effective amount of a pharmaceutical composition to a subject, wherein the pharmaceutical composition includes a tropic cell that carries a modified oncolytic virus, wherein the virus comprises a tumor selective promoter element and/or a capsid protein that binds a tumor-specific cell surface molecule.

What is claimed is: 
     
         1 . A method of killing a tumor cell comprising: contacting the tumor cell with a tropic cell that carries a modified oncolytic virus, wherein the virus comprises a tumor selective promoter element and/or a capsid protein that binds a tumor-specific cell surface molecule. 
     
     
         2 . The method of  claim 1 , wherein the tropic cell is an embryonic stem cell (ESC), embryonic germ cell (ESG), induced pluripotent stem cell (iPSC), embryonic carcinoma cell (ECC), bone marrow stem cell, adult stem cell, hematopoietic stem cell, neural stem cell or mesenchymal stem cell. 
     
     
         3 . The method of  claim 1 , wherein the modified oncolytic virus is a modified conditionally replicating adenovirus (CRAd). 
     
     
         4 . The method of  claim 1 , wherein the tumor selective promoter element is a survivin promoter, a cyclooxygenase-2 (COX-2) promoter, prostate specific antigen (PSA) promoter, a CXCR4 promoter, or a STAT3 promoter. 
     
     
         5 . The method of  claim 1 , wherein the capsid protein is a fiber, a penton or hexon protein. 
     
     
         6 . The method of  claim 5 , wherein the tumor specific cell surface molecule is selected from an integrin, an EGF receptor family member, a proteoglycan, a disialoganglioside, B7-H3, cancer antigen 125 (CA-125), epithelial cell adhesion molecule (EpCAM), vascular endothelial growth factor receptor 1, vascular endothelial growth factor receptor 2, carcinoembryonic antigen (CEA), a tumor associated glycoprotein, cluster of differentiation 19 (CD19), CD20, CD22, CD30, CD33, CD40, CD44, CD52, CD74, CD152, mucin 1 (MUC1), a tumor necrosis factor receptor, an insulin-like growth factor receptor, folate receptor α, transmembrane glycoprotein NMB, a C-C chemokine receptor, prostate specific membrane antigen (PSMA), recepteur d'origine nantais (RON) receptor, and cytotoxic T-lymphocyte antigen 4. 
     
     
         7 . The method of  claim 1 , wherein the tumor cell is part of a brain tumor, breast tumor, bone tumor, bladder tumor, tumor of the urinary tract, carcinoma, cervical tumor, colon tumor, esophageal tumor, gastric tumor, head and neck tumor, hepatocellular tumor, liver tumor, lung tumor, lymphoma and leukemia, melanoma, ovarian tumor, pancreatic tumor, pituitary tumor, prostate tumor, rectal tumor, renal tumor, sarcoma, testicular tumor, thyroid tumor, and uterine tumor. 
     
     
         8 . A method of killing a brain tumor cell comprising contacting the brain tumor cell with a neural stem cell that carries a modified conditionally replicating adenovirus (CRAd) which comprises a tumor selective promoter element and/or a fiber protein that binds heparan sulfate proteoglycans. 
     
     
         9 . The method of  claim 8 , wherein the brain tumor cell is a glioma cell 
     
     
         10 . The method of  claim 8 , wherein the neural stem cell is from a neural stem cell line HB1.F3-CD. 
     
     
         11 . The method of  claim 8 , wherein the tumor selective promoter is a survivin promoter. 
     
     
         12 . A method of treating cancer comprising administering, to a subject, a therapeutically effective amount of a pharmaceutical composition which comprises a tropic cell that carries a modified oncolytic virus, wherein the virus comprises a tumor selective promoter element and/or a capsid protein that binds a tumor-specific cell surface molecule. 
     
     
         13 . The method of  claim 12 , further comprising administering one or more therapeutic agent in combination with the pharmaceutical composition. 
     
     
         14 . The method of  claim 13 , wherein the one or more therapeutic agent is temozolomide (TMZ), radiotherapy or both. 
     
     
         15 . The method of  claim 12 , wherein the tropic cell is a neural stem cell. 
     
     
         16 . The method of  claim 12 , wherein the modified oncolytic virus is a modified conditionally replicating adenovirus (CRAd). 
     
     
         17 . The method of  claim 12 , wherein the tumor selective promoter element is a survivin promoter. 
     
     
         18 . The method of  claim 12 , wherein the capsid protein is a fiber, a penton or hexon protein. 
     
     
         19 . The method of  claim 17 , wherein the tumor specific cell surface molecule is a heparan sulfate proteoglycan. 
     
     
         20 . The method of  claim 12 , wherein the cancer treated is a glioma.