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US 9,862,932 B2Granted
Oncolytic virus therapy for resistant tumors
AssigneeThe General Hospital Corporation
InventorsKhalid Shah, Kaoru Tamura, Hiroaki Wakimoto
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AssigneeThe General Hospital Corporation
InventorsKhalid Shah, Kaoru Tamura, Hiroaki Wakimoto
Estimating the term…
Disclosed herein is a recombinant oncolytic virus comprising a nucleic acid sequence encoding tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). One such oncolytic virus is oHSV. One form of TRAIL contained within the oncolytic virus is a secreted form of TRAIL. Examples of various forms of oHSV and secreted TRAIL are disclosed therein. Also disclosed are host cells and therapeutic formulations comprising the recombinant oncolytic virus. Also disclosed are methods of treating cancer in a subject by administering a therapeutic formulation comprising the recombinant oncolytic virus to the subject.
A recombinant oncolytic herpes simplex virus (oHSV) comprising a nucleic acid sequence encoding, in expressible form, a polypeptide comprising the extracellular domain of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) fused to an isoleucine zipper and the extracellular domain of hFlt3 ligand, wherein the oHSV is selected from the group consisting of G47Δ, HSV-R3616, 1716, R3616, and R4009, and wherein the recombinant oncolytic herpes simplex virus induces apoptosis in tumor cells that are resistant to apoptosis induction by TRAIL and by oncolytic herpes simplex virus.
A pharmaceutical composition comprising a recombinant oncolytic herpes simplex virus (oHSV) comprising a nucleic acid sequence encoding, in expressible form, a polypeptide comprising the extracellular domain of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) fused to an isoleucine zipper and the extracellular domain of hFlt3 ligand, and a pharmaceutically acceptable carrier, wherein the oHSV is selected from the group consisting of G47Δ, HSV-R3616, 1716, R3616, and R4009, and wherein the recombinant oncolytic herpes simplex virus induces apoptosis in tumor cells that are resistant to apoptosis induction by TRAIL and by oncolytic herpes simplex virus.
Dependencies are inferred from the claim text.