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

Patent metadata

Field	Value
Publication number	US-10744172-B2
Application number	US-201916369886-A
Country	US
Kind code	B2
Filing date	Mar 29, 2019
Priority date	Dec 10, 2012
Publication date	Aug 18, 2020
Grant date	Aug 18, 2020

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, the method comprising administering to the subject a therapeutically effective amount of a composition comprising an adenovirus, wherein:
(a) the adenovirus comprises a genome encoding a melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) protein;
(b) the adenovirus binds desmoglein-2 or CD46;
(c) the adenovirus is replication competent in cancer cells; and
(d) the cancer is a prostate cancer, a pancreatic cancer, or a glioblastoma.

2. The method of claim 1 , wherein the mda-7/IL-24 protein is encoded within an E3 region of the adenovirus genome.

3. The method of claim 1 , wherein the adenovirus comprises a viral capsid knob of a serotype 3 adenovirus.

4. The method of claim 1 , wherein the adenovirus is a recombinant serotype 5 adenovirus.

5. The method of claim 4 , wherein the adenovirus is an adenovirus serotype 5/serotype 3 chimera (Ad.5/3).

6. The method of claim 1 , wherein viral replication of the adenovirus is under the control of a cancer-selective promoter.

7. The method of claim 6 , wherein the cancer-selective promoter is a Progression Elevated Gene (PEG)-3 promoter.

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

9. The method of claim 8 , wherein said virus is encapsulated in microbubbles in a physiologically acceptable carrier.

10. The method of claim 1 , wherein the cancer is a prostate cancer.

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

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

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

14. The method of claim 13 , wherein said at least one additional therapeutic agent is selected from the group consisting of an agent that augments reactive oxygen (ROS) production, an HDAC inhibitor, and an MCL-1 inhibitor.

15. The method of claim 13 , wherein the additional agent is perillyl alcohol.

16. The method of claim 15 , wherein the cancer is a pancreatic cancer.

17. The method of claim 13 , wherein the additional agent is sodium valproate or suberohydroxamic acid.

18. The method of claim 17 , wherein the cancer is a glioblastoma.

19. The method of claim 13 , wherein the additional agent is sabutoclax.

20. The method of claim 19 , wherein the cancer is a prostate cancer.

Assignees

• Univ Virginia Commonwealth

Inventors

• Fisher Paul
• Sarkar Devanand
• Dent Paul

Classifications

• A61K31/045 Primary

  Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates · CPC title

• A61K2039/5254

  avirulent or attenuated · CPC title

• A61K35/768 Primary

  Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766 · CPC title

• A61K2039/55511

  Organic adjuvants · CPC title

• A61P35/00

  Antineoplastic agents · CPC title