Recombinant herpes virus and pharmaceutical composition containing the same

Patent metadata

Field	Value
Publication number	US-11219651-B2
Application number	US-201514611643-A
Country	US
Kind code	B2
Filing date	Feb 2, 2015
Priority date	Feb 19, 2010
Publication date	Jan 11, 2022
Grant date	Jan 11, 2022

Abstract

A recombinant herpes virus showing high antitumor activity is provided. In particular, a recombinant herpes simplex virus that expresses an ICP6 gene under control of a tumor-specific promoter or tissue-specific promoter on the genome of the virus is provided.

First claim

The invention claimed is:

1. A recombinant herpes simplex virus-1 comprising an endogenous large subunit of ribonucleotide reductase (ICP6) gene functionally linked to a tumor-specific promoter or a tissue-specific promoter, wherein the tumor-specific promoter or the tissue-specific promoter is heterologous to the ICP6 gene.

2. The recombinant herpes simplex virus-1 according to claim 1 , wherein the tumor-specific promoter or the tissue-specific promoter is a promoter selected from the group consisting of a human telomerase reverse transcriptase (hTERT) promoter, a prostate-specific enhancer sequence (PSES) promoter, and an osteocalcin (OC) promoter.

3. The recombinant herpes simplex virus-1 according to claim 1 , wherein a γ34.5 gene and/or an ICP47 gene is deleted or inactivated.

4. The recombinant herpes simplex virus-1 according to claim 3 , wherein the γ34.5 gene is deleted or inactivated.

5. The recombinant herpes simplex virus-1 according to claim 3 , wherein the ICP47 gene is deleted or inactivated.

6. The recombinant herpes simplex virus-1 according to claim 3 , wherein the γ34.5 gene is deleted or inactivated and the ICP47 gene is deleted or inactivated.

7. A pharmaceutical composition comprising the recombinant herpes simplex virus-1 as claimed in claim 1 as an active ingredient.

8. The pharmaceutical composition according to claim 7 , which is a therapeutic agent for a tumor.

9. The pharmaceutical composition according to claim 8 , wherein the tumor is selected from the group consisting of tumors with a low growth rate, benign tumors, and tumors with low ribonucleotide reductase activity.

10. The pharmaceutical composition according to claim 8 , wherein the tumor is selected from the group consisting of prostate cancer, kidney cancer, breast cancer, chondrosarcoma, and meningioma.

11. A method of treating a tumor in a subject, comprising administering a therapeutically effective amount of the recombinant herpes simplex virus-1 as claimed in claim 1 directly to the tumor in the subject.

12. The recombinant herpes simplex virus-1 according to claim 1 , wherein the endogenous ICP6 gene is functionally linked to the tissue-specific promoter.

13. The recombinant herpes simplex virus-1 according to claim 1 , wherein the recombinant herpes simplex virus-1 exhibits high replication ability in tumor cells having low ribonucleotide reductase (RR) activity as compared to an HSV construct having a deleted or inactivated ICP6 gene.

14. The recombinant herpes simplex virus-1 according to claim 13 , wherein the HSV construct is T-01 or G474.

15. The recombinant herpes simplex virus-1 according to claim 13 , wherein the tumor cells having a low ribonucleotide reductase (RR) activity are kidney cancer OSRC2 cells or DU145 prostate cancer cells.

16. An oncolytic therapeutic comprising a recombinant herpes simplex virus-1 having an endogenous large subunit of ribonucleotide reductase (ICP6) gene functionally linked to a tumor-specific promoter or a tissue-specific promoter, wherein the tumor-specific promoter or the tissue-specific promoter is heterologous to the ICP6 gene, and one or both the γ34.5 genes being inactivated or deleted.

Assignees

• Univ Tokyo

Inventors

• Todo Tomoki
• Fukuhara Hiroshi

Classifications

• C12N2830/008

  cell type or tissue specific enhancer/promoter combination · CPC title

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• C12N2710/16671

  Demonstrated in vivo effect · CPC title

• C12N15/86

  Viral vectors · CPC title

• C12N2710/16632

  Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent · CPC title