Tropism modified cancer terminator virus (Ad.5/3 CTV;AD.5/3-CTV-M7)

Patent metadata

Field	Value
Publication number	US-10314870-B2
Application number	US-201314650775-A
Country	US
Kind code	B2
Filing date	Dec 10, 2013
Priority date	Dec 10, 2012
Publication date	Jun 11, 2019
Grant date	Jun 11, 2019

Abstract

A tropism modified cancer terminator virus (Ad.5/3-CTV; Ad.5/3-CTV-M7) has been found to have infectivity that is Coxsackie Adenoviral Receptor (CAR) independent. The Ad.5/3-CTV (Ad.5/3-CTV-M7) may be used alone or in combination with other therapeutic agents such as agents that augment reactive oxygen (ROS) production, HDAC inhibitors, MCL-1 inhibitors and Bcl-2 inhibitors to treat a variety of cancers particularly including malignant glioma (GBM), renal cancer, prostate cancer, and colorectal cancer.

First claim

We claim:

1. A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of composition comprising a cancer terminator virus (CTV) comprising an adenovirus serotype 5/serotype 3 chimera (Ad.5/3), wherein (i) the virus expresses melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24); (ii) viral replication is under control of the Progression Elevated Gene (PEG)-3 promoter; and (iii) the cancer is a prostate cancer, a pancreatic cancer, or a glioblastoma.

2. The method of claim 1 wherein said administering is performed systemically.

3. The method of claim 2 wherein said virus is encapsulated in microbubbles in a physiologically acceptable carrier.

4. The method of claim 1 , further comprising administering to the patient at least one additional therapeutic agent.

5. The method of claim 4 wherein said at least one additional therapeutic agent is selected from the group consisting of agents that augment reactive oxygen (ROS) production, HDAC inhibitors, MCL-1 inhibitors, and Bcl-2/Bcl-xL inhibitors.

6. The method of claim 1 wherein said cancer is a low-Coxsackie-Adeno virus Receptor (CAR) cancer.

7. The method of claim 1 , wherein the cancer is a pancreatic cancer.

8. The method of claim 7 , further comprising administering perillyl alcohol to the subject.

9. The method of claim 1 , wherein the cancer is a glioblastoma.

10. The method of claim 9 , further comprising administering an HDAC inhibitor to the subject.

11. The method of claim 1 , wherein said cancer is a prostate cancer.

12. The method of claim 11 , further comprising administering an MCL-1 inhibitor to the subject.

13. The method of claim 1 , wherein said cancer is a high-Coxsackie-Adeno virus Receptor (CAR) cancer.

14. The method of claim 4 , wherein said at least one additional therapeutic agent is selected from the group consisting of perillyl alcohol, an HDAC inhibitor, and an MCL-1 inhibitor.

Assignees

• Univ Virginia Commonwealth

Inventors

• Fisher Paul
• Sarkar Devanand
• Dent Paul

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C12N2710/10343

  viral genome or elements thereof as genetic vector · CPC title

• A61K31/404

  Indoles, e.g. pindolol · CPC title

• C12N2710/10321

  Viruses as such, e.g. new isolates, mutants or their genomic sequences · CPC title