Method of targeting oncolytic viruses to tumors

Abstract

The present invention pertains to a strategy of selectively targeting oncolytic virotherapy, using either naturally occurring or genetically modified viruses by packaging them in mesenchymal stem cells (MSCs). The present invention concerns MSCs, compositions comprising the MSCs, and methods of using the MSCs for treatment of cancer and for lysing or inducing apoptosis of cancer cells in vitro or in vivo.

We claim: 
     
         1 . A mesenchymal stem cell (MSC) that over-expreses interferon-beta and is indoleamine 2,3-dioxygenase (IDO)-deficient. 
     
     
         2 . The MSC of  claim 1 , wherein the MSC is infected with a naturally occurring or genetically modified virus. 
     
     
         3 . The MSC of  claim 2 , wherein the virus is an oncolytic virus. 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . The MSC of  claim 1 , wherein the MSC is a human MSC. 
     
     
         7 . (canceled) 
     
     
         8 . A method for treating cancer, comprising administering an effective amount of the MSC of  claim 1  to a human or non-human animal subject in need thereof. 
     
     
         9 . The method of  claim 8 , wherein the cancer is lung cancer. 
     
     
         10 . The method of  claim 9 , wherein the lung cancer is non-small cell lung cancer (NSCLC). 
     
     
         11 . The method of  claim 8 , further comprising administering an inhibitor of indoleamine 2,3-dioxygenase (IDO inhibitor) to the subject. 
     
     
         12 - 20 . (canceled) 
     
     
         21 . A pharmaceutical composition comprising the MSC of  claim 1 . 
     
     
         22 . The pharmaceutical composition of  claim 21 , further comprising an inhibitor of indoleamine 2,3-dioxygenase (IDO inhibitor). 
     
     
         23 . The pharmaceutical composition of  claim 21 , further comprising an adjuvant. 
     
     
         24 . The MSC of  claim 1 , wherein the MSC is IDO-deficient due to deletion or gene silencing. 
     
     
         25 . The MSC of  claim 1 , wherein the MSC is IDO-deficient due to an IDO inhibitor. 
     
     
         26 . The MSC of  claim 25 , wherein the IDO inhibitor is selected from the group consisting of a tryptophan analog, a naphthoquinone based inhibitor, hydroxyamidine, an interfering RNA specific for IDO1 and/or IDO2, NLG919, and combinations thereof.