Oncolytic rhabdovirus expressing IL12
Disclosed herein is an oncolytic recombinant Maraba virus whose genome comprises one or more nucleic acid sequences that, in combination, encode an interleukin-12 (IL12) protein or a functional portion thereof. A method for treating a cancer in a patient using the oncolytic recombinant Maraba virus is also disclosed. The present disclosure also provides a tumour cell infected with an oncolytic rhabdovirus whose genome comprises one or more nucleic acid sequences that, in combination, encode an interleukin-12 (IL12) protein or a functional portion thereof, for use as an infected cell vaccine (ICV) for the treatment of a cancer. A method for treating a cancer in a patient using the infected cell vaccine is also disclosed.
1. An oncolytic Maraba virus comprising a genome that comprises, from 3′ end to 5′ end, nucleic acid sequences encoding an N, a P, an M, a G, and an L protein, and one or more nucleic acid sequences that, alone or in combination, are capable of expressing a human interleukin-12 (IL12) protein or a functional portion thereof, wherein the one or more nucleic acid sequences that, alone or in combination, are capable of expressing a human IL12 protein is/are located in the genome between the 3′ end and the nucleic acid sequences encoding the N, P, M, G, and L proteins, in between the nucleic acid sequences encoding the N and the P proteins, in between the nucleic acid sequences encoding the P and the M proteins, in between the nucleic acid sequences encoding the M and the G, or between the '5 end and the nucleic acid sequences encoding the N, P, M, G and L proteins.
2. The Maraba virus of claim 1 , wherein the virus comprises a substitution at amino acid 242 of the wild type G protein.
3. The Maraba virus of claim 2 , wherein the amino acid at position 242 is an arginine.
4. The Maraba virus of claim 1 , wherein the virus comprises a substitution at amino acid 123 of the wild type M protein.
5. The Maraba virus of claim 4 , wherein the amino acid at position 123 is a tryptophan.
6. The Maraba virus of claim 3 , wherein the Maraba virus is the MG1 Maraba virus.
7. The Maraba virus of claim 1 , wherein the human IL12 protein comprises an amino acid sequence that is at least 80% identical to the wild type human IL12 sequence.
8. The Maraba virus of claim 7 , wherein the human IL12 protein comprises an amino acid sequence that is at least 90% identical to the wild type human IL12 sequence.
9. The Maraba virus of claim 8 , wherein the human IL12 protein comprises an amino acid sequence that is identical to the wild type human IL12 sequence.
10. The Maraba virus of claim 1 , wherein the human IL12 protein comprises the p40 and p35 subunits.
11. The Maraba virus of claim 10 , wherein the p40 protein comprises the amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 2.
12. The Maraba virus of claim 11 , wherein the p40 protein comprises the amino acid sequence of SEQ ID NO: 2.
13. The Maraba virus of claim 10 , wherein the p35 protein comprises the amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 1.
14. The Maraba virus of claim 10 , wherein the p35 protein comprises the amino acid sequence of SEQ ID NO: 1.
15. The Maraba virus of claim 1 , wherein the functional portion of the IL12 protein is a portion that is capable of stimulating the growth of T cells or NK cells.
16. The Maraba virus of claim 1 , wherein the functional portion of the IL12 protein is capable of stimulating the production of IFN-gamma.
17. A method for treating a cancer in a patient, the method comprising administering to the patient the oncolytic Maraba virus of claim 1 .
18. The method of claim 17 , wherein the virus comprises a substitution at amino acid 242 of the wild type G protein.
19. The method of claim 18 , wherein the amino acid at position 242 is an arginine.
20. The method of claim 19 , wherein the virus comprises a substitution at amino acid 123 of the wild type M protein.
21. The method of claim 20 , wherein the amino acid at position 123 is a tryptophan.
22. The method of claim 21 , wherein the Maraba virus is the MG1 Maraba virus.
23. The method of claim 22 , wherein the human IL12 protein comprises an amino acid sequence that is at least 80% identical to the wildtype human IL12 sequence.
24. The method of claim 23 , wherein the human IL12 protein comprises an amino acid sequence that is at least 90% identical to the wild type human IL12 sequence.
25. The method of claim 24 , wherein the human IL12 protein comprises an amino acid sequence that is identical to the wild type human IL12 sequence.
26. The method of claim 25 , wherein the human IL12 protein comprises the p40 and p35 subunits.
27. The method of claim 26 , wherein the p40 protein comprises the amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 2.
28. The method of claim 27 , wherein the p40 protein comprises the amino acid sequence of SEQ ID NO: 2.
29. The method of claim 26 , wherein the p35 protein comprises the amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 1.
30. The method of claim 29 , wherein the p35 protein comprises the amino acid sequence of SEQ ID NO: 1.
31. The method of claim 17 , wherein the functional portion of the IL12 protein is a portion that is capable of stimulating the growth of T cells or NK cells.
32. The method of claim 17 , wherein the functional portion of the IL12 protein is capable of stimulating the production of IFN-gamma.
33. The method of claim 17 , wherein the virus is administered intravenously, intraperitonealy, intrathecally, intracranially, subcutaneously or intrathoracically.
34. The method of claim 33 , wherein the virus is administered intravenously.