This document provides methods and materials related to vesicular stomatitis viruses. For example, vesicular stomatitis viruses, nucleic acid molecules encoding VSV polypeptides, methods for making vesicular stomatitis viruses, and methods for using vesicular stomatitis viruses to treat cancer are provided.

This document provides methods and materials related to vesicular stomatitis viruses. For example, vesicular stomatitis viruses, nucleic acid molecules encoding VSV polypeptides, methods for making vesicular stomatitis viruses, and methods for using vesicular stomatitis viruses to treat cancer are provided.

The present invention relates to high-titer hybrid vims vectors which produce virus-like vesicle (VLVs) and compositions and methods thereof for targeting a malignancy or infectious disease. VLVs are a capsid-free, self-replicating artificial virus platform carrying positive-strand capped and polyadenylated RNA encoding an in vitro evolved Semliki Forest vims (SFV) RNA-dependent RNA replicase and the vesicular stomatitis virus (VSV) glycoprotein. The VLVs of the present invention and pharmaceutical compositions thereof encode for polynucleotide and/or polypeptide therapeutic agents useful in methods for the treatment, prophylaxis, and prevention of malignancies and infectious diseases.

The present invention relates to high-titer hybrid vims vectors which produce virus-like vesicle (VLVs) and compositions and methods thereof for targeting a malignancy or infectious disease. VLVs are a capsid-free, self-replicating artificial virus platform carrying positive-strand capped and polyadenylated RNA encoding an in vitro evolved Semliki Forest vims (SFV) RNA-dependent RNA replicase and the vesicular stomatitis virus (VSV) glycoprotein. The VLVs of the present invention and pharmaceutical compositions thereof encode for polynucleotide and/or polypeptide therapeutic agents useful in methods for the treatment, prophylaxis, and prevention of malignancies and infectious diseases.

The present disclosure relates to a method for stimulating tumor antigen-specific immune responses comprising cancer vaccination involving the blockade or inhibition of interferon signaling. In particular, the method comprises administering an inhibitor of interferon signaling and a cancer vaccine comprising a tumor antigen, wherein the inhibitor of interferon signaling is administered before the cancer vaccine.

The present disclosure concerns an oncolytic virus for the treatment of cancer, such as in brain cancer, for example glioblastoma. The oncolytic virus may exhibit reduced levels of neurotoxicity. The oncolytic virus may be an isolated viral particle capable of producing a cDNA polynucleotide that includes a sequence according to SEQ ID NO: 1 when the virus is in a host cell. The oncolytic virus may be an isolated viral particle that includes an RNA polynuclotide that includes a sequence according to SEQ ID NO: 2. The oncolytic virus may be an isolated viral particle having a genome that includes open reading frames that encode: proteins having sequences comprising SEQ ID NOs: 3, 4, 5, 6 and 7; or variants thereof.

The present disclosure concerns an oncolytic virus for the treatment of cancer, such as in brain cancer, for example glioblastoma. The oncolytic virus may exhibit reduced levels of neurotoxicity. The oncolytic virus may be an isolated viral particle capable of producing a cDNA polynucleotide that includes a sequence according to SEQ ID NO: 1 when the virus is in a host cell. The oncolytic virus may be an isolated viral particle that includes an RNA polynuclotide that includes a sequence according to SEQ ID NO: 2. The oncolytic virus may be an isolated viral particle having a genome that includes open reading frames that encode: proteins having sequences comprising SEQ ID NOs: 3, 4, 5, 6 and 7; or variants thereof.

Some embodiments of the present disclosure are directed to methods that include delivering to a subject a nucleic acid encoding an antigen, wherein the nucleic acid is delivered via a tumor-selective vehicle or via intratumoral injection, and delivering to the subject an immune cell expressing a receptor that binds to the antigen.

Some embodiments of the present disclosure are directed to methods that include delivering to a subject a nucleic acid encoding an antigen, wherein the nucleic acid is delivered via a tumor-selective vehicle or via intratumoral injection, and delivering to the subject an immune cell expressing a receptor that binds to the antigen.

Herein is provided a recombinant tumor-selective viral particle comprising a nucleic acid encoding a recombinant polypeptide for directing an extracellular vesicle (EV) to at least one target cell, said recombinant polypeptide comprising: at least one targeting moiety for directing said EV to said at least one target molecule expressed by said at least one target cell; at least one EV-anchoring polypeptide; and at least one intravesicular polypeptide. The viral particle may be from an oncolytic viruses. Recombinant polypeptides for programming EVs to target particular molecules are also provided. Also described are therapeutic EVs for delivering payload polypeptides (and/or cargo molecules) to target cells, e.g., in vaccine or cell-free “CAR-T”-like applications, along with EVs for recruiting immune cells to target cells in EV-mediated BiTE -like applications. Oncolytic viruses may also be engineered to infect tumor cells and shed programmed EVs, yielding additional therapeutic effects.