Mumps virus as a potential oncolytic agent

1. A recombinant mumps virus (MuV) having oncolytic anti-cancer activity, wherein said recombinant MuV comprises nucleic acid selected from the group consisting of nucleic acid encoding a modified V protein comprising a H to Y substitution at amino acid 203 as numbered in SEQ ID NO: 4, nucleic acid encoding a modified matrix (M) protein comprising a L to O substitution at amino acid 338 as numbered in SEQ ID NO:6, nucleic acid encoding a modified fusion (F) protein comprising a Y to S substitution at amino acid 430 as numbered in SEQ ID NO:7, and nucleic acid encoding a modified hemagglutinin-neuraminidase (HN) protein comprising a L to I substitution at amino acid 522 as numbered in SEQ ID NO:9.

2. The recombinant MuV of claim 1 , wherein said recombinant MuV is a replication competent MuV.

3. The recombinant MuV of claim 1 , wherein said recombinant MuV comprises nucleic acid encoding a modified V protein comprising a H to Y substitution at amino acid 203 as numbered in SEQ ID NO: 4, and wherein said modification in a V protein coding sequence comprises a C to T substitution at nucleotide 2585 as numbered in SEQ ID NO:1.

4. The recombinant MuV of claim 1 , wherein said recombinant MuV comprises nucleic acid encoding a modified M protein comprising a L to O substitution at amino acid 338 as numbered in SEQ ID NO:6, and wherein said modification in a M protein coding sequence comprises a C to A substitution at nucleotide 4275 as numbered in SEQ ID NO:1.

5. The recombinant MuV of claim 1 , wherein said recombinant MuV comprises nucleic acid encoding a modified F protein comprising a Y to S substitution at amino acid 430 as numbered in SEQ ID NO:7, and wherein said modification in a F protein coding sequence comprises a A to C substitution at nucleotide 5834 as numbered in SEQ ID NO:1.

6. The recombinant MuV of claim 1 , wherein said recombinant MuV comprises nucleic acid encoding a modified HN protein comprising a L to I substitution at amino acid 522 as numbered in SEQ ID NO:9, and wherein said modification in a HN protein coding sequence comprises a C to A substitution at nucleotide 8177 as numbered in SEQ ID NO:1.

7. The recombinant MuV of claim 1 , wherein said recombinant MuV comprises nucleic acid encoding a modified V protein comprising a H to Y substitution at amino acid 203 as numbered in SEQ ID NO: 4, nucleic acid encoding a modified M protein comprising a L to O substitution at amino acid 338 as numbered in SEQ ID NO:6, nucleic acid encoding a modified F protein comprising a Y to S substitution at amino acid 430 as numbered in SEQ ID NO:7, and nucleic acid encoding a modified HN protein comprising a L to I substitution at amino acid 522 as numbered in SEQ ID NO:9.

8. A method for treating a patient having cancer, the method comprising:

administering to the patient a recombinant mumps virus (MuV) having oncolytic anticancer activity, wherein said recombinant MuV comprises nucleic acid selected from the group consisting of nucleic acid encoding a modified V protein comprising a H to Y substitution at amino acid 203 as numbered in SEQ ID NO: 4, nucleic acid encoding a modified matrix (M) protein comprising a L to O substitution at amino acid 338 as numbered in SEQ ID NO:6, nucleic acid encoding a modified fusion (F) protein comprising a Y to S substitution at amino acid 430 as numbered in SEQ ID NO:7, and nucleic acid encoding a modified hemagglutinin-neuraminidase (HN) protein comprising a L to I substitution at amino acid 522 as numbered in SEQ ID NO:9.

9. The method of claim 8 , wherein the cancer is a blood cancer selected from leukemia, lymphoma, or myeloma.

10. The method claim 9 , wherein the blood cancer is myeloma.

11. The method of claim 8 , wherein the cancer is a carcinoma selected from prostate cancer, breast cancer, hepatocellular carcinoma, lung cancer, or colorectal carcinoma.

12. The method of claim 11 , wherein the carcinoma is colorectal carcinoma.

13. The method of claim 8 , wherein said recombinant MuV is a replication competent MuV.

14. The method of claim 8 , wherein said recombinant MuV comprises nucleic acid encoding a modified V protein comprising a H to Y substitution at amino acid 203 as numbered in SEQ ID NO: 4, and wherein said modification in a V protein coding sequence comprises a C to T substitution at nucleotide 2585 as numbered in SEQ ID NO:1.

15. The method of claim 8 , wherein said recombinant MuV comprises nucleic acid encoding a modified M protein comprising a L to O substitution at amino acid 338 as numbered in SEQ ID NO:6, and wherein said modification in a M protein coding sequence comprises a C to A substitution at nucleotide 4275 as numbered in SEQ ID NO:1.

16. The method of claim 8 , wherein said recombinant MuV comprises nucleic acid encoding a modified F protein comprising a Y to S substitution at amino acid 430 as numbered in SEQ ID NO:7, and wherein said modification in a F protein coding sequence comprises a A to C substitution at nucleotide 5834 as numbered in SEQ ID NO:1.

17. The method of claim 8 , wherein said recombinant MuV comprises nucleic acid encoding a modified HN protein comprising a L to I substitution at amino acid 522 as numbered in SEQ ID NO:9, and wherein said modification in a HN protein coding sequence comprises a C to A substitution at nucleotide 8177 as numbered in SEQ ID NO:1.

18. The method of claim 8 , wherein said recombinant MuV comprises nucleic acid encoding a modified V protein comprising a H to Y substitution at amino acid 203 as numbered in SEQ ID NO: 4, nucleic acid encoding a modified M protein comprising a L to O substitution at amino acid 338 as numbered in SEQ ID NO:6, nucleic acid encoding a modified F protein comprising a Y to S substitution at amino acid 430 as numbered in SEQ ID NO:7, and nucleic acid encoding a modified HN protein comprising a L to I substitution at amino acid 522 as numbered in SEQ ID NO:9.

19. The method of claim 8 , further comprising administering ruxolitinib.