Method of inducing an oncolytic effect on tumor cells using Zika virus

Patent metadata

Field	Value
Publication number	US-10786537-B2
Application number	US-201716322396-A
Country	US
Kind code	B2
Filing date	Aug 17, 2017
Priority date	Aug 18, 2016
Publication date	Sep 29, 2020
Grant date	Sep 29, 2020

Abstract

The present invention provide for methods of inducing an oncolytic effect on tumor cells using Zika virus. The invention also provides for inducing an oncolytic effect on brain tumors and treating brain tumors, and in particular, glioblastomas and neuroblastoma. The treatment involves the administration of Zika virus, which has an oncolytic effect on the tumor cells.

First claim

What is claimed is:

1. A method of treating a glioma, comprising:
administering, via intra-tumoral delivery, intra-cerebral delivery, intracarotid delivery, intravenous delivery or subcutaneous delivery, a composition comprising a quantity of Zika virus for a multiplicity of infection (MOI) of about 1-100 or a quantity of Zika virus of about 10e3 to 10e11 to a subject in need thereof to treat the glioma.

2. The method of claim 1 , wherein the Zika virus is an Asian genotype Zika virus or an African genotype Zika virus.

3. The method of claim 2 , wherein the Asian genotype Zika virus comprises a genome represented by the sequence disclosed in GenBank accession number KU501215 (clinical isolate PRVABC59).

4. The method of claim 1 , wherein the glioma is a glioblastoma.

5. The method of claim 1 , wherein administering the composition comprises intra-tumoral delivery, intra-cerebral delivery, intracarotid delivery, or a combination thereof.

6. The method of claim 1 , wherein administering the composition comprises intravenous delivery or subcutaneous delivery.

7. The method of claim 1 , further comprising administering an additional brain tumor therapy.

8. A method of inducing an oncolytic effect on a brain tumor glioma, comprising:
administering, via intra-tumoral delivery, intra-cerebral delivery, intracarotid delivery, intravenous delivery or subcutaneous delivery, a composition comprising a quantity of Zika virus for a multiplicity of infection (MOI) of about 1-100 or a quantity of Zika virus of about 10e3 to 10e11 to a subject in need thereof to induce the oncolytic effect on the brain tumor glioma.

9. The method of claim 8 , wherein the Zika virus is an Asian genotype Zika virus or an African genotype virus.

10. The method of claim 9 , wherein the Asian genotype Zika virus comprises a genome represented by the sequence disclosed in to GenBank accession number KU501215 (clinical isolate PRVABC59).

11. The method of claim 8 , wherein the glioma is a glioblastoma.

12. The method of claim 8 , wherein administering the composition comprises intra-tumoral delivery, intra-cerebral delivery, intracarotid delivery, or a combination thereof.

13. The method of claim 8 , wherein administering the composition comprises intravenous delivery or subcutaneous delivery.

14. The method of claim 8 , further comprising administering an additional brain tumor therapy.

15. A method of inducing an oncolytic effect on a tumor glioma, comprising:
administering, via intra-tumoral delivery, intra-cerebral delivery, intracarotid delivery, intravenous delivery or subcutaneous delivery, a composition comprising a quantity of Zika virus for a multiplicity of infection (MOI) of about 1-100 or a quantity of Zika virus of about 10e3 to 10e11 to a subject in need thereof to induce the oncolytic effect on the glioma,
wherein the tumor expresses a flaviviral cell entry receptor selected from the group consisting of GRP78, SDC2, HSP90AB1, TYRO2, AXL, MERTK and combinations thereof.

16. The method of claim 15 , wherein the Zika virus is an Asian genotype Zika virus or an African genotype Zika virus.

17. The method of claim 16 , wherein the Asian genotype Zika virus comprises a genome represented by the sequence disclosed in to GenBank accession number KU501215 (clinical isolate PRVABC59).

Assignees

• Cedars Sinai Medical Center

Inventors

• Arumugaswami Vaithilingaraja
• Breunig Joshua

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• A61K35/768 Primary

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

• C12N2770/24132

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