Newcastle disease viruses and uses thereof
Described herein are chimeric Newcastle disease viruses comprising a packaged genome comprising a transgene encoding interleukin-12. The chimeric Newcastle disease viruses and compositions thereof are useful in combination with an antagonist of programmed cell death protein 1 (“PD-1”) or a ligand thereof in the treatment of cancer. In particular, described herein are methods for treating cancer comprising administering the chimeric Newcastle disease viruses in combination with an antagonist of PD-1 or a ligand thereof, wherein the chimeric Newcastle disease virus comprises a packaged genome comprising a transgene encoding interleukin-12.
1. A chimeric NDV comprising a packaged genome, said packaged genome comprising a transgene encoding a human IL-12, wherein the transgene comprises the corresponding negative sense RNA sequence of the nucleotide sequence set forth in SEQ ID NO:61 or 26.
2. A chimeric NDV comprising a packaged genome, said packaged genome comprising a transgene encoding a human IL-12, wherein the IL-12 comprises the amino acid sequence set forth in SEQ ID NO:43 or 42.
3. The chimeric NDV of claim 2 , wherein the transgene comprises the corresponding negative sense RNA sequence of the nucleotide sequence set forth in SEQ ID NO:63, 68, 53, or 66.
4. The chimeric NDV of claim 1 , wherein the chimeric NDV comprises an NDV backbone of LaSota strain and the packaged genome comprises a nucleotide sequence encoding a mutated F protein with the amino acid mutation L289A, wherein the mutated F protein is incorporated into the virion of the chimeric NDV.
5. The chimeric NDV of claim 1 , wherein the packaged genome comprises a transcription unit for an NDV NP gene, a transcription unit for an NDV P gene, a transcription unit for an NDV M gene, a transcription unit for an NDV F gene, a transcription unit for an NDV HN gene, and a transcription unit for an NDV L gene, and wherein the transgene is inserted between the NDV P gene and the NDV M gene of the packaged genome.
6. The chimeric NDV of claim 1 , wherein the packaged genome comprises the nucleotide sequence set forth in SEQ ID NO:51.
7. The chimeric NDV of claim 2 , wherein the packaged genome comprises the nucleotide sequence set forth in SEQ ID NO:52 or 60.
8. A pharmaceutical composition comprising the chimeric NDV of claim 1 , in an admixture with a pharmaceutically acceptable carrier.
9. A pharmaceutical composition comprising the chimeric NDV of claim 2 , in an admixture with a pharmaceutically acceptable carrier.