Targeted vectors for cancer immunotherapy

Abstract

This invention provides compositions and methods for treating cancer. More specifically this invention is directed to a targeted retroviral vector comprising a cytokine gene that can be administered either alone or in combination with a targeted retroviral vector comprising a cytocidal gene for treating cancer in a subject. Also provided are a kit or drug delivery system comprising the compositions for use in the methods described.

What is claimed is:  
     
         1 . A targeted retroviral vector particle comprising a modified viral surface protein for targeting the vector and a cytokine gene.  
     
     
         2 . The targeted retroviral particle of  claim 1 , wherein the modified viral surface protein is targeting the extracellular matrix or tumor vasculature.  
     
     
         3 . The targeted retroviral particle of  claim 1 , wherein the modified viral surface protein is targeting the extracellular matrix.  
     
     
         4 . The targeted retroviral particle of  claim 3 , wherein the modified viral surface protein is targeting a collagen binding motif.  
     
     
         5 . The targeted retroviral particle of  claim 4 , wherein the modified viral surface protein is targeting the Von Willebrand coagulation factor.  
     
     
         6 . The targeted retroviral particle of  claim 3 , wherein the modified viral surface protein is targeting tumor vasculature.  
     
     
         7 . The targeted retroviral particle of  claim 1 , wherein the cytokine gene is selected from the group consisting of IL-1, TNF, IL-2, IFN-γ, IL-4, IL-7 and GM-CSF.  
     
     
         8 . The targeted retroviral particle of  claim 7 , wherein the cytokine gene is GM-CSF.  
     
     
         9 . A pharmaceutical composition comprising the targeted retroviral vector of  claim 1 .  
     
     
         10 . A method for inhibiting cancer in a subject comprising administering to the subject an effective amount of the pharmaceutical composition of  claim 9 .  
     
     
         11 . The pharmaceutical composition of  claim 9 , further comprising a targeted retroviral vector particle comprising a modified viral surface protein for targeting the vector and a cytocidal gene.  
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein targeted retroviral particle comprising a modified viral surface protein for targeting the vector and a cytocidal gene is targeting the extracellular matrix or tumor vasculature.  
     
     
         13 . The pharmaceutical composition of  claim 11 , wherein the cytocidal gene is selected from the group consisting of tumor suppressor genes, thymidine kinases or mutated cyclin genes.  
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the mutated cyclin gene is a dominant negative mutation of a cyclin G1 gene.  
     
     
         15 . A method for inhibiting cancer in a subject comprising administering to the subject an effective amount of the pharmaceutical composition of  claim 11 .  
     
     
         16 . A composition comprising a targeted retroviral vector particle comprising a modified viral surface protein for targeting the vector to the Von Willebrand coagulation factor and a cytokine gene and a targeted retroviral vector particle comprising a modified viral surface protein for targeting the vector to the Von Willebrand coagulation factor and a cytocidal gene.  
     
     
         17 . The composition of  claim 16 , wherein the cytocidal gene is a mutated cyclin gene.  
     
     
         18 . The composition of  claim 17 , wherein the cytocidal gene is a dominant negative mutation of the cyclin G1 gene.  
     
     
         19 . The composition of  claim 16 , wherein the cytokine is selected from the group consisting of IL-1, TNF, IL-2, IFN-γ, IL-4, IL-7 and GM-CSF.  
     
     
         20 . The composition of  claim 19 , wherein the cytokine is GM-CSF.  
     
     
         21 . The composition of  claim 16 , further comprising a pharmaceutical excipient.  
     
     
         22 . A method for inhibiting cancer in a subject comprising administering to the subject an effective amount of the pharmaceutical composition of claim  21 .