Oncolytic virus platform to treat hematological cancer

Patent metadata

Field	Value
Publication number	US-2021252086-A1
Application number	US-201917274051-A
Country	US
Kind code	A1
Filing date	Sep 4, 2019
Priority date	Sep 5, 2018
Publication date	Aug 19, 2021
Grant date	—

Abstract

The disclosure provides Myxoma vims that expresses one or more immunomodulatory transgenes and its use in inhibit-mg and/or treating a hematological cancer in a subject. The disclosure also provides a leukocyte having a Myxoma virus that expresses one or more immunomodulatory transgenes and the use of the leukocyte for inhibiting and/or treating a hematological cancer in a subject.

First claim

We claim:

1 . A myxoma virus (MYXV) comprising one or more immunomodulatory transgenes, wherein the one or more immunomodulatory transgenes encode BiKE (Bi-specific Natural Killer and Neutrophil engager), LIGHT (Lymphotoxins-like, exhibits Inducible expression, and competes with HSV Glycoprotein D for Herpesvirus entry mediator (HVEM), a receptor expressed by T lymphocytes), Decorin, or a combination thereof.

2 . The myxoma virus of claim 1 , wherein the myxoma virus comprises MYXV-BiKE.

3 . The myxoma virus of claim 1 or claim 2 , wherein the BiKE binds to an antigen present on a natural killer cell, a neutrophil, or a combination thereof.

4 . The myxoma virus of any one of claims 1 - 3 , wherein the BiKE binds to an antigen present on a hematologic cancer cell.

5 . The myxoma virus of any one of claims 1 - 4 , wherein the BiKE binds to an antigen present on a myeloma cell.

6 . The myxoma virus of any one of claims 1 - 5 , wherein the BiKE binds to an antigen present on a leukemia cell.

7 . The myxoma virus of any one of claims 1 - 6 , wherein the BiKE binds to an antigen present on a lymphoma cell.

8 . The myxoma virus of any one of claims 1 - 7 , wherein the BiKE binds to CD16.

9 . The myxoma virus of any one of claims 1 - 8 , wherein the BiKE binds CD138.

10 . The myxoma virus of any one of claims 1 - 9 , wherein the BiKE comprises one or more single chain variable fragments (scFvs).

11 . The myxoma virus of any one of claims 1 - 10 , wherein the BiKE comprises one or more humanized single chain variable fragments (scFvs).

12 . The myxoma virus of any one of claims 1 - 11 , wherein the BiKE comprises a sequence that is at least 70% identical to any one of SEQ ID NOs: 6 or 16-31.

13 . The myxoma virus of any one of claims 1 - 12 , wherein the BiKE is between the M135 and M136 open reading frames of the myxoma virus genome.

14 . The myxoma virus of any one of claims 1 - 13 , wherein the myxoma virus comprises MYXV-huBiKE-GFP.

15 . The myxoma virus of claim 1 , wherein the myxoma virus comprises MYXV-LIGHT.

16 . The myxoma virus of claim 15 , wherein the LIGHT comprises a sequence from human LIGHT.

17 . The myxoma virus of claim 15 or claim 16 , wherein the LIGHT comprises a sequence that is at least 70% identical to any one of SEQ ID NOs: 13-15.

18 . The myxoma virus of any one of claims 15 - 17 , wherein the LIGHT is between the M135 and M136 open reading frames of the myxoma virus genome.

19 . The myxoma virus of any one of claim 1 or 15 - 18 , wherein the myxoma virus comprises MYXV-FLuc-huLIGHT-TdTomato.

20 . The myxoma virus of claim 1 , wherein the myxoma virus comprises MYXV-Decorin.

21 . The myxoma virus of claim 20 , wherein the Decorin comprises a sequence from human Decorin.

22 . The myxoma virus of claim 20 , wherein the Decorin comprises a sequence from mouse Decorin.

23 . The myxoma virus of any one of claims 20 - 22 , wherein the Decorin comprises a sequence that is at least 70% identical to any one of SEQ ID NOs: 7-12.

24 . The myxoma virus of any one of claims 20 - 23 , wherein the Decorin is between the M135 and M136 open reading frames of the myxoma virus genome.

25 . The myxoma virus of claim 16 , wherein the myxoma virus comprises MYXV-mDecorin-GFP.

26 . The myxoma virus of any of claims 1 - 25 , further comprising a reporter gene.

27 . The myxoma virus of claim 26 , wherein the reporter gene is a fluorescent protein.

28 . The myxoma virus of claim 27 , wherein the reporter gene is a luminescent substrate or enzyme.

29 . The myxoma virus of any one claims 1 - 28 , further comprising a deletion in the myxoma virus genome.

30 . The myxoma virus of any one of claims 1 - 29 , wherein the myxoma virus comprises a deletion or disruption of one or more genes selected from the group consisting of M001R, M002R, M003.1R, M003.2R, M004.1R, M004R, M005R, M006R, M007R, M008.1R, M008R, M009L, M013, M036L, M063L, M11L, M128L, M131R, M135R, M136R, M141R, M148R, M151R, M152R, M153R, M154L, M156R, M-T2, M-T4, M-T5, M-T7, and SOD.

31 . The myxoma virus of any one of claims 1 - 30 , wherein the myxoma virus comprises a deletion of M135.

32 . A composition comprising the myxoma virus of any one of claims 1 - 31 and a pharmaceutically acceptable carrier.

33 . A method of treating a hematological cancer in a subject in need thereof, comprising administering to the subject a myxoma virus that comprises one or more immunomodulatory transgenes.

34 . The method of claim 33 , wherein the one or more immunomodulatory transgenes comprise BiKE, LIGHT, Decorin, or a combination thereof.

35 . The method of claim 33 or claim 34 , wherein the myxoma virus comprises MYXV-BiKE.

36 . The method of claim 34 or claim 35 , wherein the BiKE binds to an antigen present on a natural killer cell, a neutrophil, or a combination thereof.

37 . The method of any one of claims 34 - 36 , wherein the BiKE binds to an antigen present on a hematologic cancer cell.

38 . The method of any one of claims 34 - 37 , wherein the BiKE binds to an antigen present on a myeloma cell.

39 . The method of any one of claims 34 - 37 , wherein the BiKE binds to an antigen present on a leukemia cell.

40 . The method of any one of claims 34 - 37 , wherein the BiKE binds to an antigen present on a lymphoma cell.

41 . The method of any one of claims 34 - 40 , wherein the BiKE binds to CD16.

42 . The method of any one of claims 34 - 41 , wherein the BiKE binds CD138.

43 . The method of any one of claims 34 - 42 , wherein the BiKE comprises one or more single chain variable fragments (scFvs).

44 . The method of any one of claims 34 - 43 , wherein the BiKE comprises one or more humanized single chain variable fragments (scFvs).

45 . The method of any one of claims 34 - 44 , wherein the BiKE comprises a sequence that is at least 70% identical to any one of SEQ ID NOs: 6 or 16-31.

46 . The method of any one of claims 34 - 45 , wherein the BiKE is between the M135 and M136 open reading frames of the myxoma virus genome.

47 . The method of any one of claims 34 - 46 , wherein the myxoma virus comprises MYXV-huBiKE-GFP.

48 . The method of claim 33 or claim 34 , wherein the myxoma virus comprises MYXV-LIGHT.

49 . The method of claim 32 or claim 48 , wherein the LIGHT comprises a sequence from human LIGHT.

50 . The method of any one of claim 34 , 48 , or 49 , wherein the LIGHT comprises a sequence that is at least 70% identical to any one of SEQ ID NOs: 13-15.

51 . The method of any one of claim 34 or 48 - 50 , wherein the LIGHT is between the M135 and M136 open reading frames of the myxoma virus genome.

52 . The method of any one of claim 34 or 48 - 51 , wherein the myxoma virus comprises MYXV-FLuc-huLIGHT-TdTomato.

53 . The method of claim 33 or claim 34 , wherein the myxoma virus comprises MYXV-De

Assignees

• Univ Arizona State

Inventors

• Mcfadden Douglas Grant
• Torres-Dominguez Lino
• Villa Nancy
• Rahman Mohammed Masmudur

Classifications

• A61K40/50

  characterised by the use of allogeneic cells · CPC title

• A61K40/42

  Cancer antigens · CPC title

• A61K40/10

  characterised by the cell type used · CPC title

• A61K2239/31

  characterized by the route of administration · CPC title

• C12N2710/24032

  Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent · CPC title