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.

1 - 19 . (canceled) 
     
     
         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 detergent or a surfactant as 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 20  wherein the delivery enhancing agent is the surfactant. 
     
     
         28 . The method of  claim 20  wherein the delivery-enhancing agent is the 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.times. the critical micellization concentration. 
     
     
         39 . (canceled)