The present disclosure provides a recombinant oncolytic myxoma vims engineered to express a soluble form of an immune checkpoint protein in conjunction with a cytokine/chemokine and/or a tumor antigen. In certain aspects, the oncolytic myxoma virus is a replication competent virus such as myxoma vims. Methods of cancer treatment comprising administering the recombinant oncolytic myxoma virus expressing the soluble form of the immune checkpoint protein are also provided.

The present disclosure provides a recombinant oncolytic myxoma vims engineered to express a soluble form of an immune checkpoint protein in conjunction with a cytokine/chemokine and/or a tumor antigen. In certain aspects, the oncolytic myxoma virus is a replication competent virus such as myxoma vims. Methods of cancer treatment comprising administering the recombinant oncolytic myxoma virus expressing the soluble form of the immune checkpoint protein are also provided.

Compounds, compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo. Also disclosed are pharmaceutical compositions comprising a Cbl-b inhibitor and a cancer vaccine, as well as methods for treating cancer using a Cbl-b inhibitor and a cancer vaccine; and pharmaceutical compositions comprising a Cbl-b inhibitor and an oncolytic virus, as well as methods for treating cancer using a Cbl-b inhibitor and an oncolytic virus.

Compounds, compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo. Also disclosed are pharmaceutical compositions comprising a Cbl-b inhibitor and a cancer vaccine, as well as methods for treating cancer using a Cbl-b inhibitor and a cancer vaccine; and pharmaceutical compositions comprising a Cbl-b inhibitor and an oncolytic virus, as well as methods for treating cancer using a Cbl-b inhibitor and an oncolytic virus.

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.

This invention provides a vaccinia virus that induces cell fusion between infected cells and a method for producing the same. Such vaccinia virus is deprived of the K2L gene or the HA gene or functions of the K2L gene and the HA gene and is mutated to induce cell fusion between infected cells and induce cell death.

This invention provides a vaccinia virus that induces cell fusion between infected cells and a method for producing the same. Such vaccinia virus is deprived of the K2L gene or the HA gene or functions of the K2L gene and the HA gene and is mutated to induce cell fusion between infected cells and induce cell death.

Provided is an M1 virus. Further provided are a series of uses of said virus. The uses include, but are not limited to, viral vectors, anti-tumor agents, and pharmaceutical compositions. Said virus can effectively inhibit the growth of various tumor cells, and at the same time, has tumor targeting properties and is non-toxic to normal cells. Said virus can be administrated by means of intravenous injection, having operational convenience.

Provided is an M1 virus. Further provided are a series of uses of said virus. The uses include, but are not limited to, viral vectors, anti-tumor agents, and pharmaceutical compositions. Said virus can effectively inhibit the growth of various tumor cells, and at the same time, has tumor targeting properties and is non-toxic to normal cells. Said virus can be administrated by means of intravenous injection, having operational convenience.