Avirulent oncolytic herpes simplex virus strains engineered to counter the innate host response
First Claim
1. An avirulent, oncolytic herpes simplex virus having an intact Us12 gene and an endogenous Us11 gene expressed as a late gene, wherein said virus is modified from the wild-type herpes simplex virus with both γ
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134.5 genes of the virus being deleted and Us11 genes that are expressed as immediate-early (IE) genes being inserted into the γ
134.5 gene locus in place of both γ
134.5 genes.
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Abstract
The present invention relates to an avirulent, oncolytic herpes simplex virus modified from a wild-type herpes simplex virus so that both γ134.5 genes of the virus have been deleted and each replaced with an interferon-resistance gene that is expressed as an immediate-early gene. The present invention also relates to a pharmaceutical composition that includes the modified herpes simplex virus of the present invention and a pharmaceutically acceptable vehicle for in situ administration to tumor cells. Also provided in the present invention are methods for killing tumor cells in a subject and for immunizing a subject against an infectious disease, cancer, or an autoimmune disease that involve administering to a subject the modified avirulent, oncolytic herpes simplex virus of the present invention.
68 Citations
13 Claims
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1. An avirulent, oncolytic herpes simplex virus having an intact Us12 gene and an endogenous Us11 gene expressed as a late gene, wherein said virus is modified from the wild-type herpes simplex virus with both γ
-
134.5 genes of the virus being deleted and Us11 genes that are expressed as immediate-early (IE) genes being inserted into the γ
134.5 gene locus in place of both γ
134.5 genes. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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134.5 genes of the virus being deleted and Us11 genes that are expressed as immediate-early (IE) genes being inserted into the γ
Specification