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US 12,274,724 B2Granted
Methods for treatment of cancer using chikungunya-VSV chimeric virus
AssigneeYale University
InventorAnthony N. van den Pol
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AssigneeYale University
InventorAnthony N. van den Pol
Estimating the term…
Chimeric viruses having a vesicular stomatitis virus (VSV) background where the VSV G protein is supplemented or replaced with an alphavirus glycoprotein(s), or a functional fragment(s) thereof, are provided. A preferred alphavirus is Chikungunya virus. In particular embodiments, the glycoprotein(s) is or includes E3, E2, K6, and E1 proteins of an alphavirus, preferably Chikungunya virus. Methods of using the chimeric viruses for treatment of cancers, particularly brain cancers and metastasis thereof are also provided. In some embodiments, the chimeric viruses retain superior oncolytic activity to infect and destroy cancer cells selectively, such as glioblastoma and intracranial melanoma metastases. In some embodiments, the chimeric viruses have reduced toxicity to e.g., heathy cells relative to a control such as the parent VSV with the VSV G protein.
A method of treating cancer in a subject comprising administering to a subject with cancer a pharmaceutical composition comprising an effective amount of a chimeric vesicular stomatitis virus (VSV) to treat cancer in the subject, wherein the chimeric VSV comprises a VSV background with Chikungunya virus glycoproteins in place of the VSV glycoprotein (G), wherein the chimeric VSV genome comprises nucleic acid sequences encoding a VSV nucleocapsid protein (N), a VSV phosphoprotein (P), a VSV matrix (M) protein, a VSV large (L) viral polymerase, and Chikungunya virus E3, E2, 6K, and E1 proteins.
Dependencies are inferred from the claim text.