Oncolytic Herpes Simplex Virus and Therapeutic Uses Thereof
First Claim
1. A variant herpes simplex virus (HSV) having an intact endogenous Us12 encoding gene and an intact endogenous Us11 encoding gene, lacking functional ICP34.5 encoding genes,wherein each ICP34.5 encoding gene is replaced by a polynucleotide cassette comprising:
- (a) a Us11 encoding gene operably associated with an immediate early (IE) promoter; and
(b) at least one heterologous gene encoding a polypeptide capable of enhancing an anti-tumor response.
1 Assignment
0 Petitions
Accused Products
Abstract
The present invention relates to variants of herpes simplex virus (HSV) that selectively infect and replicate in cancer cells, including HSV strains that selectively infect and replicate in bladder cancer cells. Preferred HSV of the invention have intact endogenous Us11 and Us12 genes and have genes encoding ICP34.5 replaced with a gene encoding Us11 fused to an HSV immediate early (IE) promoter. The variant HSV of the invention also comprise one or more additional heterologous genes encoding immunomodulatory polypeptides. Methods and compositions using these variant HSV, e.g. for example, for treating cancer in a subject, are also provided.
-
Citations
33 Claims
-
1. A variant herpes simplex virus (HSV) having an intact endogenous Us12 encoding gene and an intact endogenous Us11 encoding gene, lacking functional ICP34.5 encoding genes,
wherein each ICP34.5 encoding gene is replaced by a polynucleotide cassette comprising: -
(a) a Us11 encoding gene operably associated with an immediate early (IE) promoter; and (b) at least one heterologous gene encoding a polypeptide capable of enhancing an anti-tumor response. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 16, 17, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33)
-
-
12. A variant herpes simplex virus (HSV) having an intact endogenous Us12 encoding gene and an intact endogenous Us11 encoding gene, lacking functional ICP34.5 encoding genes,
wherein each ICP34.5 encoding gene is replaced by a polynucleotide cassette comprising: -
(a) a Us11 encoding gene operably associated with an immediate early (IE) promoter; and (b) a gene encoding an inhibitor of antigen presentation on class I major histocompatibility complex (MHC) molecules, wherein said inhibitor is capable of inhibiting antigen presentation on the surface of virally infected tumor cells. - View Dependent Claims (13, 14, 15, 18)
-
-
19. A variant herpes simplex virus (HSV) having an intact endogenous Us12 encoding gene and an intact endogenous Us11 encoding gene, lacking functional ICP34.5 encoding genes, wherein each ICP34.5 encoding gene is replaced with a polynucleotide cassette comprising a nucleic acid sequence set forth in one of SEQ ID NO:
- 21, SEQ ID NO;
22, SEQ ID NO;
23, SEQ ID NO;
24 and SEQ ID NO;
25.
- 21, SEQ ID NO;
-
20. A variant herpes simplex virus (HSV) having a genome sequence set forth in SEQ ID NO:
- 26, SEQ ID NO;
27, SEQ ID NO;
28, SEQ ID NO;
29, or SEQ ID NO;
30.
- 26, SEQ ID NO;
Specification