Transluminal delivery of oncoltyic viruses for cancer therapy
Inventors
Assignees
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Publication Number
US-9675673-B2
Publication Date
2017-06-13
Expiration Date
Abstract
Methods, apparatus and compositions are provided for treatment of cancer of a selected organ by intraluminal delivery of oncolytic agents through a blood vessel or duct leading to the cancer tissue. During the time the oncolytic agents are being applied to the targeted tissue downstream, the designated vessel or duct can be selectively occluded to increase concentration and pressure of the applied agents at the target site. Oncolytic compositions including oncolytic viruses formulated with delivery visualization markers are provided.
Core Innovation
The invention relates to methods for treating cancer tissue in an organ by delivering an oncolytic virus selected for susceptibility to infect the cancer tissue. The virus is applied locally to the cancer tissue by application of the virus proximally through an infusion lumen of a balloon catheter inserted into a blood vessel or duct in direct fluid communication with a target site of the cancer tissue, and discharging the virus under relatively low pressure distally from the infusion lumen directly into the blood vessel or duct proximally of the site and distally of a single balloon of the catheter.
The selectively increased pressure forces the virus under an effective extravasation pressure through a natural endothelial barrier of the blood vessel or duct lining and into the cancer tissue at the target site. This is described as increasing local delivery of an effective dose of the virus to the target site of the cancer tissue. The approach is configured to use the catheter geometry in which a single balloon is located proximally of the target delivery region, while the distal discharge occurs under relatively low pressure.
A related inventive concept is described for delivering parvoviruses to a tumor by intraluminal application through a central lumen of a single-balloon catheter inserted into a blood vessel or duct. Inflating the single balloon located proximally of a distal exit is used in combination with an effective extravasation pressure so that parvoviruses are selectively delivered from the distal exit through the natural endothelial lining and into a parenchyma at a tumor site located distally of the distal exit. Dependent refinements described in the document include occluding the blood vessel or duct with the balloon to increase parvovirus concentration or volume and locally administering interferons together with the parvoviruses to increase parvovirus concentration or volume and thereby support extravasation pressure.
Claims Coverage
The partial content includes two independent claims: one for a general oncolytic virus method for treating cancer tissue in an organ, and one for delivering parvoviruses to a tumor using a single-balloon catheter with an effective extravasation pressure. Across these independent claims, the inventive coverage centers on intraluminal balloon-catheter delivery with proximal pressure boosting and selective extravasation through a natural endothelial barrier, with specific refinements for parvovirus agents and interferon co-administration in dependent claims.
Intraluminal balloon-catheter delivery with effective extravasation pressure
A method for treating cancer tissue in an organ comprising delivering an oncolytic virus locally to cancer tissue by applying the virus proximally through an infusion lumen of a balloon catheter inserted into a blood vessel or duct in direct fluid communication with a target site, discharging the virus under relatively low pressure distally from the infusion lumen into the blood vessel or duct proximally of the site and distally of a single balloon, and selectively increasing pressure in the blood vessel or duct by the concentration or volume of virus delivered to force the virus under an effective extravasation pressure through a natural endothelial barrier into the cancer tissue at the target site, thereby increasing local delivery of an effective dose.
Single-balloon catheter parvovirus delivery through natural endothelial lining
A method for delivering parvoviruses to a tumor comprising intraluminal application of the parvoviruses through a central lumen of a single-balloon catheter inserted into a blood vessel or duct, using an effective extravasation pressure to result in selective delivery of an effective dose from a distal exit of the catheter central lumen directly through a natural endothelial lining of the blood vessel or duct and into a parenchyma at the tumor site located distally of the distal exit, after having inflated the single balloon located proximally of the distal exit.
The independent-claim coverage is grounded in balloon-catheter intraluminal delivery where proximal pressure increase via virus concentration or volume enables selective extravasation through a natural endothelial barrier into tumor-associated tissue at a distal site. The second independent claim narrows the delivery agent to parvoviruses and specifies the single-balloon catheter and distal-exit selective delivery into tumor parenchyma after proximal balloon inflation.
Stated Advantages
Increases local delivery of an effective dose of the virus to the target site of the cancer tissue.
Allows selective delivery of an effective dose of parvoviruses to a tumor site via delivery through a natural endothelial lining.
Documented Applications
Delivering oncolytic viruses locally to cancer tissue in an organ by intraluminal balloon-catheter application to a target site in direct fluid communication with the cancer tissue.
Delivering parvoviruses to a tumor in a patient's body by intraluminal application using a single-balloon catheter with effective extravasation pressure.
Local cancer delivery routes explicitly discussed in the document include brain via arterial circulation, kidney via renal artery, pancreas via ductus Wirsungii, and liver via bile duct using ERCP/PTC, each described with balloon occlusion and pressure-mediated extravasation.
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