Transluminal Delivery of Viruses for Treatment of Diseased Tissue

Abstract

Methods are provided for treatment of cancer in a subject's body by intraluminal delivery of oncolytic viruses through a balloon catheter or alternative mechanism inserted in a blood vessel or duct leading to a target site of the cancer tissue, or for somatic cell gene therapy of single defective gene-caused other diseases or disorders by similar intraluminal delivery of non-oncolytic viruses to a target site of affected tissue and cells of the disease or disorder, wherein during delivery of the oncolytic or non-oncolytic virus, the designated vessel or duct is selectively occluded at both ends of the target site by two spaced-apart inflated balloons of the catheter to block perfusion therethrough and allow control of the volume of virus delivered to the target site so as to increase concentration and pressure of the virus thereat sufficient to enable viral penetration of an endothelial barrier of the vessel or duct without compromise thereof and into diseased cells in the vicinity of the target site toward achieving a desired therapy.

1 . A method for treating a disease or disorder in the body of a subject, said method comprising the steps of:
 (a) occluding a blood vessel or duct of the body bounding a target site of defective cells of affected tissue of the disease or disorder with two balloons and to block perfusion through the vessel or duct at the target site and to create a chamber between the balloons; and   (b) delivering an effective dose of a selected agent contained in a body-compatible fluid carrier under pressure to the chamber in the blocked portion of the vessel or duct, to control the volume delivered and thereby the pressure thereof in the blocked portion so as to reach an effective extravasation pressure sufficient to force the effective dose of the agent through the natural endothelial barrier at the lining of the vessel or duct, without inflicting damage thereto, to penetrate and induce the desired therapeutic effect in cells at the target site.   
     
     
         2 . The method of  claim 1 , wherein the agent has a diameter of 10 μm to 50 μm. 
     
     
         3 . The method of  claim 1 , wherein the agent is selected from the group consisting of viruses, unmodified or engineered exosomes, microvessicles, cytotoxic and cytostatic agents. 
     
     
         4 . The method of  claim 3 , wherein the cytotoxic and cytostatic agents are selected from: interferons, chemical compounds inducing cytotoxic/static effects, or substances modifying the immune tolerance, wherein the substances modifying the immune tolerance comprises negative co-stimulators or check point inhibitors.