Oncolytic herpes simplex virus and therapeutic uses thereof
First Claim
1. A variant oncolytic herpes simplex virus (HSV) comprising functionally inactive ICP34.5 encoding genes, wherein at least one of the ICP34.5 encoding genes is rendered functionally inactive by the insertion of an expression cassette comprising:
- (a) a US11 encoding polynucleotide operably associated with an immediate early (IE) promoter;
(b) a virus-derived heterologous transporter associated with antigen presentation (TAP) inhibitor encoding polynucleotide; and
(c) a Interleukin-12 (IL-12) encoding polynucleotide.
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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, for example, for treating cancer in a subject, are also provided.
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Citations
40 Claims
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1. A variant oncolytic herpes simplex virus (HSV) comprising functionally inactive ICP34.5 encoding genes, wherein at least one of the ICP34.5 encoding genes is rendered functionally inactive by the insertion of an expression cassette comprising:
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(a) a US11 encoding polynucleotide operably associated with an immediate early (IE) promoter; (b) a virus-derived heterologous transporter associated with antigen presentation (TAP) inhibitor encoding polynucleotide; and (c) a Interleukin-12 (IL-12) encoding polynucleotide. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40)
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Specification