Compositions and methods for therapeutic use

Abstract

A method and pharmaceutical composition for the treatment of cancer using a gene delivery system, such as a viral vector delivery system, comprising a therapeutic gene such as p53 or a retinoblastoma tumor suppressor gene wherein the gene delivery system is formulated in a buffer comprising a delivery-enhancing agent such as ethanol or a detergent.

What is claimed is:  
     
         1 . A method of administering a therapeutic agent to a tissue having an epithelial membrane, comprising administering a therapeutically effective amount of the therapeutic agent formulated in a buffer comprising a detergent.  
     
     
         2 . The method of  claim 1 , wherein the therapeutic agent is a protein.  
     
     
         3 . The method of  claim 1 , wherein the therapeutic agent is a nucleic acid.  
     
     
         4 . The method of  claim 3 , wherein the nucleic acid is a tumor suppressor gene.  
     
     
         5 . The method of  claim 1 , wherein the detergent is Big CHAP.  
     
     
         6 . The method of  claim 1 , wherein the detergent is TRITON® X-100.  
     
     
         7 . The method of  claim 1 , wherein the therapeutic agent is a tumor suppressor gene.  
     
     
         8 . The method of  claim 7 , wherein the tumor suppressor gene is p53.  
     
     
         9 . The method of  claim 7 , wherein the tumor suppressor gene is a retinoblastoma gene.  
     
     
         10 . The method of  claim 1 , wherein the concentration of the detergent is about 0.5-2× the critical micellization concentration.  
     
     
         11 . A pharmaceutical composition comprising a therapeutically effective amount of a therapeutic agent formulated in a buffer comprising a detergent.  
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein the therapeutic agent is a protein.  
     
     
         13 . The pharmaceutical composition of  claim 11 , wherein the therapeutic agent is a nucleic acid.  
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the nucleic acid is a tumor suppressor gene.  
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the tumor suppressor gene is p53.  
     
     
         16 . The pharmaceutical composition of  claim 14 , wherein the tumor suppressor gene is a retinoblastoma gene.  
     
     
         17 . The pharmaceutical composition of  claim 11 , wherein the detergent is Big CHAP.  
     
     
         18 . The pharmaceutical composition of  claim 11 , wherein the detergent is TRITON® X-100 detergent.  
     
     
         19 . The pharmaceutical composition of  claim 11 , wherein the concentration of the detergent is about 0.5-2× the critical micellization concentration.  
     
     
         20 . A method of treating bladder cancer comprising administration of a therapeutically effective amount of a therapeutic gene contained within a gene delivery system that is formulated in a buffer comprising a delivery-enhancing agent.  
     
     
         21 . The method of  claim 20  wherein the gene delivery system is a viral vector delivery system.  
     
     
         22 . The method of  claim 20  wherein the gene delivery system is a recombinant adenoviral vector delivery system.  
     
     
         23 . The method of  claim 20  wherein the therapeutic gene is a tumor suppressor gene.  
     
     
         24 . The method of  claim 23  wherein the tumor suppressor gene is a retinoblastoma tumor suppressor gene.  
     
     
         25 . The method of  claim 23  wherein the tumor suppressor gene is p53.  
     
     
         26 . The method of  claim 20  wherein the delivery-enhancing agent is an alcohol.  
     
     
         27 . The method of  claim 26  wherein the alcohol is ethanol.  
     
     
         28 . The method of  claim 20  wherein the delivery-enhancing agent is a detergent.  
     
     
         29 . The method of  claim 28 , wherein the detergent is Big CHAP.  
     
     
         30 . The method of  claim 28 , wherein the detergent is TRITON® X-100.  
     
     
         31 . The method of  claim 20  wherein the administration is by intravesical administration.  
     
     
         32 . The method of  claim 20  wherein the therapeutically effective amount of a therapeutic gene contained within a gene delivery system is in the range of about from 1×10 8  particles/ml to 5×10 11  particles/ml of a recombinant adenovirus in which the therapeutic gene is inserted.  
     
     
         33 . The method of  claim 20  wherein the therapeutically effective amount of a therapeutic gene contained within a gene delivery system is in the range of about from 1×10 9  particles/ml to 1×10 11  particles/ml of a recombinant adenovirus in which the therapeutic gene is inserted.  
     
     
         34 . The method of  claim 24  wherein the retinoblastoma tumor suppressor gene encodes full length RB protein.  
     
     
         35 . The method of  claim 24  wherein the retinoblastoma tumor suppressor gene encodes p56 RB .  
     
     
         36 . The method of  claim 22  wherein the delivery-enhancing agent is administered prior to administration of the recombinant viral vector delivery system comprising the therapeutic gene.  
     
     
         37 . The method of  claim 22  wherein the delivery-enhancing agent is administered with the recombinant viral vector delivery system comprising the therapeutic gene.  
     
     
         38 . The method of  claim 28  wherein the concentration of the detergent is 0.5-2× the critical micellization concentration.  
     
     
         39 . A pharmaceutical formulation for administration of a recombinant adenovirus, comprising about 10 9 -10 11  PN/ml recombinant adenovirus, about 2-10 mM Big CHAP or about 0.1-1.0 mM TRITON®-X-100 detergent, phosphate buffered saline (PBS), about 2-3% sucrose (w/v) and about 1-3 mM MgCl 2 , about pH 6.4-8.4.