RNA viruses for immunovirotherapy

Patent metadata

Field	Value
Publication number	US-10933106-B2
Application number	US-201515121751-A
Country	US
Kind code	B2
Filing date	Feb 24, 2015
Priority date	Feb 25, 2014
Publication date	Mar 2, 2021
Grant date	Mar 2, 2021

Abstract

The present invention relates to a recombinant virus of the family Paramyxoviridae, comprising at least one expressible polynucleotide encoding a secreted activator of the immune response, to a polynucleotide encoding the same, and to a kit comprising the same. Moreover, the present invention relates to a method for treating cancer in a subject afflicted with cancer, comprising contacting said subject with a recombinant virus of the family Paramyxoviridae of the invention, and thereby, treating cancer in a subject afflicted with cancer.

First claim

The invention claimed is:

1. A polynucleotide encoding a recombinant virus of the family Paramyxoviridae, the polynucleotide comprising the nucleic acid sequence of SEQ ID NO: 6, 7, 8, and/or 9, wherein the recombinant virus comprises at least one expressible polynucleotide encoding a secreted activator of the immune response.

2. The polynucleotide of claim 1 , wherein said recombinant virus is a recombinant Morbillivirus.

3. The polynucleotide of claim 2 , wherein said recombinant Morbillivirus is a recombinant measles virus (MV).

4. The polynucleotide of claim 3 , wherein the recombinant MV is derived from vaccine strain Schwarz (Edmonston A).

5. The polynucleotide of claim 1 , wherein the secreted activator of the immune response is a ligand for an immune checkpoint blockade protein.

6. The polynucleotide of claim 1 , wherein the secreted activator of the immune response is a secreted antagonistic single-chain antibody against CTLA 4.

7. The polynucleotide of claim 6 , wherein the secreted antagonistic single-chain antibody against CTLA-4 comprises the amino acid sequence of SEQ ID NO:1.

8. The polynucleotide of claim 1 , wherein the secreted activator of the immune response is a secreted antagonistic single-chain antibody against PD-L1.

9. The polynucleotide of claim 8 , wherein the secreted antagonistic single-chain antibody against PD-L1 comprises the amino acid sequence of SEQ ID NO:3.

10. The polynucleotide of claim 1 , further comprising a second expressible polynucleotide encoding a second secreted activator of the immune response.

11. The polynucleotide of claim 10 , wherein said second expressible polynucleotide encoding a secreted activator of the immune response is a cytokine or a second antagonist of an inhibitory factor of a T-cell or an antagonist of a negative immune regulator of the tumor-immune microenvironment.

12. A method for treating cancer in a subject afflicted with cancer, comprising
a) contacting said subject with the polynucleotide according to claim 1 , and
b) thereby, treating cancer in a subject afflicted with cancer.

13. The method of claim 12 , wherein said cancer is a solid cancer, a metastasis, or a relapse thereof.

14. The method of claim 12 , wherein treating cancer is reducing tumor burden.

15. The method of claim 12 , wherein said cancer is malignant melanoma, head and neck cancer, hepatocellular carcinoma, pancreatic carcinoma, prostate cancer, renal cell carcinoma, gastric carcinoma, colorectal carcinoma, lymphomas or leukemias.

16. A kit comprising at least the polynucleotide of claim 1 housed in a container.

17. A medicament comprising the polynucleotide of claim 1 , and at least one pharmacologically acceptable excipient.

18. An in vitro method for activating immune cells in a sample comprising cancer cells and immune cells, comprising
a) contacting said sample comprising cancer cells and immune cells with the polynucleotide according to claim 1 , and
b) thereby, activating immune cells comprised in said sample.

Assignees

• Deutsches Krebsforschung Szentrum
• Univ Heidelberg Ruprecht Karls
• Deutsches Krebsforsch

Inventors

• Engeland Christine
• Ungerechts Guy
• Bossow Sascha

Classifications

• C12N7/00 Primary

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

• C12N2760/18433

  Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory · CPC title

• A61K35/768 Primary

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

• C12N2760/18432

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

• A61K39/39558

  against tumor tissues, cells, antigens · CPC title