In one aspect, provided herein are methods for treating cancer in a subject, comprising administering to a subject an oncolytic virus (e.g., an avian paramyxovirus (AMPV)) and a vascular endothelial growth factor (VEGF)-C agent, a VEGF-D agent, or a VEGF receptor (VEGFR)-3-activating agent. In another aspect, provided herein are oncolytic viruses (e.g. APMV) comprising a genome, wherein the genome comprises a transgene that comprises a nucleotide sequence encoding a VEGF-C agent, a VEGF-D agent or a VEGF receptor (VEGFR)-3-activating agent. In another aspect, provided herein are methods for treating cancer, comprising administering to a subject an oncolytic virus (e.g. APMV), wherein the oncolytic virus comprises a genome that comprises a transgene comprising a nucleotide sequence encoding a VEGF-C agent, a VEGF-D agent, or a VEGF receptor (VEGFR)-3-activating agent.

The invention relates to a pharmaceutical formulation comprising at least three recombinant transgene expressing Newcastle Disease Virus (NDV) strains, which have been demonstrated to possess significant oncolytic activity against mammalian cancers and an improved safety profile, a non-recombinant NDV strain, a reovirus type-3 and optionally a vaccinia virus. At least one of the recombinant NDV strains comprises in its viral genome a nucleic acid sequence comprising at least one foreign gene, the at least one foreign gene encoding a checkpoint modulator, and at least one of the recombinant NDV strains comprises in its viral genome a nucleic acid sequence comprising at least one foreign gene, the at least one foreign gene encoding an angiogenesis inhibitor. The viral genome of each of the at least three recombinant NDV strains comprises a mutation in the HN gene, said mutation allowing replication of said rgNDV in a cancer cell to a higher level than replication of an otherwise identical NDV not having said mutation in the HN gene. The pharmaceutical formulation provides an improved treatment of cancer, because instead of a monotherapy, a mixture of oncolytic viruses is applied.

The invention relates to a pharmaceutical formulation comprising at least three recombinant transgene expressing Newcastle Disease Virus (NDV) strains, which have been demonstrated to possess significant oncolytic activity against mammalian cancers and an improved safety profile, a non-recombinant NDV strain, a reovirus type-3 and optionally a vaccinia virus. At least one of the recombinant NDV strains comprises in its viral genome a nucleic acid sequence comprising at least one foreign gene, the at least one foreign gene encoding a checkpoint modulator, and at least one of the recombinant NDV strains comprises in its viral genome a nucleic acid sequence comprising at least one foreign gene, the at least one foreign gene encoding an angiogenesis inhibitor. The viral genome of each of the at least three recombinant NDV strains comprises a mutation in the HN gene, said mutation allowing replication of said rgNDV in a cancer cell to a higher level than replication of an otherwise identical NDV not having said mutation in the HN gene. The pharmaceutical formulation provides an improved treatment of cancer, because instead of a monotherapy, a mixture of oncolytic viruses is applied.

The present invention provides a combination therapy of genetically modified vaccinia virus (particularly oncolytic vaccinia virus) and another cancer therapy for use in treating cancer, and a pharmaceutical composition and a combination kit for use in the therapy. More specifically, the invention provides a therapy with vaccinia virus containing a polynucleotide encoding interleukin-7 (IL-7) and a polynucleotide encoding interleukin-12 (IL-12) in combination with an immune checkpoint inhibitor, and a pharmaceutical composition and a combination kit for use in the therapy.

The present invention provides a combination therapy of genetically modified vaccinia virus (particularly oncolytic vaccinia virus) and another cancer therapy for use in treating cancer, and a pharmaceutical composition and a combination kit for use in the therapy. More specifically, the invention provides a therapy with vaccinia virus containing a polynucleotide encoding interleukin-7 (IL-7) and a polynucleotide encoding interleukin-12 (IL-12) in combination with an immune checkpoint inhibitor, and a pharmaceutical composition and a combination kit for use in the therapy.

Provided herein are variant CD80 polypeptides, immunomodulatory proteins comprising variant CD80 polypeptides, and nucleic acids encoding such proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological and oncological conditions. Compositions and methods for making and using such proteins are provided.

Provided herein are variant CD80 polypeptides, immunomodulatory proteins comprising variant CD80 polypeptides, and nucleic acids encoding such proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological and oncological conditions. Compositions and methods for making and using such proteins are provided.

The present disclosure provides a replication-competent, recombinant oncolytic vaccinia virus (RVV), compositions comprising the RVV, and use of the RVV or composition for inducing oncolysis in an individual having a tumor.

The present disclosure provides a replication-competent, recombinant oncolytic vaccinia virus (RVV), compositions comprising the RVV, and use of the RVV or composition for inducing oncolysis in an individual having a tumor.

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.