Methods and reagents for the enhancement of virus transduction in the bladder epithelium

Abstract

Agents and methods for enhancing recombinant virus transduction in the bladder epithelium are described. A first method involves contacting the luminal surface of the bladder with a composition comprising a transduction enhancing agent and an oncolytic virus. Alternatively, the luminal surface of the bladder can be contacted first with a pretreatment composition comprising a transduction enhancing agent and, subsequently, with a composition comprising an oncolytic virus. Bladder treatment compositions comprising a transduction enhancing agent and an oncolytic virus are also described.

1 - 71 . (canceled) 
     
     
         72 . A method for treating cancer of the bladder comprising:
 contacting the luminal surface of the bladder with a pretreatment composition comprising a transduction enhancing agent; and   subsequently contacting the luminal surface of the bladder with a composition comprising an oncolytic virus;   wherein the transduction enhancing agent has the following general formula:   
       
         
           
           
               
               
           
         
       
       wherein X is a sulfur or oxygen atom, each R 2  is independently hydrogen or a moiety represented by: 
       
         
           
           
               
               
           
         
       
       and R 1  represents an alkyl or alkenyl group. 
     
     
         73 . The method of  claim 72 , wherein R 1  comprises at least 12 carbon atoms. 
     
     
         74 . The method of  claim 72 , wherein each R 2  is hydrogen. 
     
     
         75 - 78 . (canceled) 
     
     
         79 . The method of  claim 72 , wherein the luminal surface of the bladder is contacted with the pretreatment composition for at least 20 minutes. 
     
     
         80 . The method of  claim 72 ; wherein the luminal surface of the bladder is contacted with the composition comprising the oncolytic virus for 15 minutes or less. 
     
     
         81 . The method of  claim 72 , wherein the luminal surface of the bladder is contacted with the composition comprising the oncolytic virus for 10 minutes or less. 
     
     
         82 . (canceled) 
     
     
         83 . The method of  claim 72 , wherein the oncoloytic virus is an oncolytic adenovirus. 
     
     
         84 . The method of  claim 83 , wherein the oncolytic adenovirus is CG8840. 
     
     
         85 . The method of  claim 72 , wherein the oncolytic virus composition comprises at least 4×10 10  viral particles. 
     
     
         86 . A method for treating cancer of the bladder comprising:
 contacting the luminal surface of the bladder with a pretreatment composition comprising a transduction enhancing agent; and   subsequently contacting the luminal surface of the bladder with a composition comprising an oncolytic virus;   wherein the transduction enhancing agent has the chemical formula:   
       
         
           
           
               
               
           
         
       
       where R 1  represents an alkyl or alkenyl group. 
     
     
         87 . The method of  claim 86 , wherein R 1  is represented by: 
       
         
           
           
               
               
           
         
       
     
     
         88 . A method of treating cancer of the bladder comprising:
 contacting the luminal surface of the bladder with a pretreatment composition comprising a transduction enhancing agent having a structure represented by the following general formula (I) or the following general formula (II):   
       
         
           
           
               
               
           
         
       
       wherein x is a positive integer; and
 subsequently contacting the luminal surface of the bladder with a composition comprising an oncolytic virus; 
 wherein x is at least 11; and 
 wherein the oncolytic virus composition comprises at least 4×10 10  viral particles. 
 
     
     
         89 . The method of  claim 88 , wherein x is 11. 
     
     
         90 . The method of  claim 89 , wherein the transduction enhancing agent has a structure represented by the general formula (I). 
     
     
         91 . The method of  claim 90 , wherein the pretreatment composition comprises about 0.1 wt. % of the transduction enhancing agent. 
     
     
         92 . The method of  claim 88 , wherein the oncolytic virus is an oncolytic adenovirus. 
     
     
         93 . The method of  claim 92 , wherein the oncolytic adenovirus is CG8840. 
     
     
         94 . A composition comprising:
 a transduction enhancing agent; and   an oncolytic virus;   wherein the transduction enhancing agent has a structure represented by the following general formula (I) or the following general formula (II):   
       
         
           
           
               
               
           
         
       
       wherein x is a positive integer; and
 wherein the concentration of the transduction enhancing agent is less than 0.025 wt/% of the composition. 
 
     
     
         95 . A method for treating cancer of the bladder comprising contacting a luminal surface of the bladder with the composition of  claim 94 . 
     
     
         96 . The method of  claim 72 , wherein the pretreatment composition comprises about 0.02 to about 0.5% by weight of the transduction enhancing agent. 
     
     
         97 . The method of  claim 72 , wherein the oncolytic virus composition further comprises a chemotherapeutic agent. 
     
     
         98 . The method of  claim 97 , wherein the chemotherapeutic agent is docetaxel. 
     
     
         99 . The method of  claim 72 , wherein contacting the luminal surface of the bladder with a pretreatment composition comprises delivering the pretreatment composition to the bladder by instillation. 
     
     
         100 . The method of  claim 99 , wherein about 50 to about 500 ml of the oncolytic virus composition is delivered to the bladder by instillation. 
     
     
         101 . The method of  claim 72 , further comprising washing the luminal surface of the bladder after contact with the pretreatment composition and before contact with the oncolytic virus composition. 
     
     
         102 . The method of  claim 72 , wherein the oncolytic virus composition comprises from about 1×10 11  to about 1×10 14  viral particles. 
     
     
         103 . The method of  claim 72 , wherein the pretreatment composition further comprises an oxidizing agent. 
     
     
         104 . The method of  claim 103 , wherein the oxidizing agent is selected from the group consisting of hypochlorous acid, hydrogen peroxide, and peroxyacetic acid.