Chimeric newcastle disease viruses and uses thereof
Described herein are chimeric Newcastle disease viruses engineered to express a heterologous interferon antagonist and compositions comprising such viruses. The chimeric Newcastle disease viruses and compositions are useful in the treatment of cancer.
1. A chimeric Newcastle disease virus (NDV), comprising a packaged genome which encodes a heterologous interferon antagonist, wherein the heterologous interferon antagonist is expressed by the virus, and wherein the packaged genome encodes a cytokine, and wherein the cytokine is expressed by the virus.
2. The chimeric NDV of claim 1 , wherein the cytokine is IL-2.
3. The chimeric NDV of claim 1 , wherein the cytokine is L-15.
4. The chimeric NDV of claim 1 , wherein the cytokine is IL-7, IL-9, IL-22, or tumor necrosis factor-beta.
5. The chimeric NDV of claim 1 , wherein the heterologous interferon antagonist is an influenza virus NS1 protein.
6. The chimeric NDV of claim 1 , wherein the heterologous interferon antagonist is a Nipah virus W protein, a Nipah virus V protein, an Ebola virus VP35 protein, a Vaccinia virus E3L protein, a respiratory syncytial virus NS2 protein, or a hepatitis C virus NS3-4 protease.
7. The chimeric NDV of claim 1 , wherein the packaged genome encodes a tumor antigen, so that the tumor antigen is expressed by the virus.
8. The chimeric NDV of claim 1 , wherein the packaged genome encodes a modified F protein that causes the chimeric NDV to be highly fusogenic, and wherein the modified F protein is expressed by the virus.
9. The chimeric NDV of claim 1 , wherein the chimeric NDV is lentogenic.
10. The chimeric NDV of claim 1 , wherein the chimeric NDV is an HUJ strain, an Ulster strain, a Hitchner B1 strain, a La Sota strain, a MET95 strain, or a B1 strain.
11. A pharmaceutical composition comprising the chimeric NDV of claim 1 and a pharmaceutically acceptable carrier.
12. A pharmaceutical composition comprising the chimeric NDV of claim 2 and a pharmaceutically acceptable carrier.
13. An isolated cell line comprising the chimeric NDV of claim 1 .
14. An isolated embryonated chicken or quail egg comprising the chimeric NDV of claim 1 .
15. A method for producing a pharmaceutical composition, the method comprising:
a. propagating the chimeric NDV of claim 1 in a cell line that is susceptible to a NDV infection; and
b. collecting the progeny virus,
wherein the virus is grown to sufficient quantities and under sufficient conditions that the virus is free from contamination, such that the progeny virus is suitable for formulation into a pharmaceutical composition.
16. A method for producing a pharmaceutical composition, the method comprising:
a. propagating the chimeric NDV of claim 1 in an embryonated chicken or quail egg; and
b. collecting the progeny virus,
wherein the virus is grown to sufficient quantities and under sufficient conditions that the virus is free from contamination, such that the progeny virus is suitable for formulation into a pharmaceutical composition.
17. A method for treating cancer in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of claim 11 .
18. A method for treating cancer in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of claim 12 .