Oncolytic rhabdovirus
Embodiments of the invention include compositions and methods related to Maraba virus and their use as anti-cancer therapeutics. Such rhabdoviruses possess tumor cell killing properties in vitro and in vivo.
1. An attenuated Maraba virus comprising:
a G protein having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:5 and an arginine at the position corresponding to position 242 of SEQ ID NO:5.
2. A method of killing a hyperproliferative cell comprising contacting the cell with an isolated oncolytic Maraba virus encoding:
a G protein having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:5 and an arginine at the position corresponding to position 242 of SEQ ID NO:5.
3. The method of claim 2 , wherein the cell is comprised in a patient.
4. The method of claim 3 , wherein the cell is a cancer cell.
5. The method of claim 4 , wherein the cancer cell is a metastatic cancer cell.
6. The method of claim 3 , wherein the oncolytic Maraba virus is administered to the patient.
7. The method of claim 6 , wherein the oncolytic Maraba virus is administered by intraperitoneal, intravenous, intra-arterial, intramuscular, intradermal, intratumoral subcutaneous, or intranasal administration.
8. The method of claim 2 , further comprising administering a second anti-cancer therapy.
9. The method of claim 8 , wherein the second cancer therapy is chemotherapeutic, radiotherapeutic, or immunotherapeutic.
10. A method for treating a cancer patient comprising administering an effective amount of an isolated oncolytic Maraba virus encoding:
a G protein having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:5 and an arginine at the position corresponding to position 242 of SEQ ID NO:5.
11. The method of claim 10 , wherein the oncolytic Maraba virus is administered intraperitoneal, intravenous, intra-arterial, intramuscular, intradermal, intratumoral, subcutaneous, or intranasal administration.
12. The method of claim 10 , further comprising administering a second cancer therapy.
13. The method of claim 12 , wherein the second cancer therapy is chemotherapy, radiotherapy, immunotherapy, or surgery.
14. A composition comprising an isolated oncolytic Maraba virus having a nucleic acid segment encoding:
a G protein having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:5 and an arginine at the position corresponding to position 242 of SEQ ID NO:5.
15. The composition of claim 14 , wherein the composition is a pharmaceutically acceptable composition.
16. The composition of claim 15 , further comprising a second anti-cancer agent.
17. The composition of claim 16 , wherein the second anti-cancer agent is a chemotherapeutic, radiotherapeutic, or immunotherapeutic.
18. The attenuated Maraba virus of claim 1 , wherein the G protein has an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 5 except for an arginine at the position corresponding to position 242 of SEQ ID NO: 5.
19. The method of claim 2 , wherein the G protein has an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 5 except for an arginine at the position corresponding to position 242 of SEQ ID NO: 5.
20. The method of claim 10 , wherein the G protein has an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 5 except for an arginine at the position corresponding to position 242 of SEQ ID NO: 5.
21. The composition of claim 14 , wherein the G protein has an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 5 except for an arginine at the position corresponding to position 242 of SEQ ID NO: 5.