Provided herein, inter alia, are oncolytic viruses that express recombinant proteins having bispecific activity. The recombinant proteins include a first fusion protein comprising a first Fc domain covalently linked to a chemokine domain, and a second Fc fusion protein comprising a second Fc domain covalently linked to an anticancer therapeutic antibody domain. The recombinant proteins and oncolytic viruses provided herein are contemplated to be effective for the treatment of cancer, particularly by trafficking immune cells to the tumor microenvironment.

The present invention provides a method and a pharmaceutical composition for the treatment of the NDO comprising the viral expression vector carrying a transcription cassette that harbors transgene(s) inhibiting/silencing neurotransmission or synaptic transmission of afferent neurons.

Provided herein are Vero cell lines that stably express Herpes Simplex Virus (HSV) ICP0 protein. These cells have the same morphology of Vero cells, exhibit stable expression of HSV ICP0 protein, and also efficiently complement replication of HSV ICP0 deficient virus for greater than 20, 30, or even 40 cell passages.

Provided is a recombinant oncolytic virus composition, comprising a first recombinant oncolytic virus and a second recombinant oncolytic virus. Both the first and second recombinant oncolytic viruses comprise a herpes simplex virus vector and an exogenous gene, the exogenous gene is encoded from one of cytokine, a monoclonal antibody having a tumor preventative and/or treatment function, tumor antigens, prodrug invertase, tumor suppressor polypeptide, antisense RNA or small RNA, wherein the exogenous genes in the first and the second recombinant oncolytic viruses are different. Also provided is an application of the recombinant oncolytic virus composition in preparation of a medicament drug for treating tumors.

An HSV vector comprising an expression cassette for one or more of IL12, IL15, and hIL15Receptor alpha subunit is provided.

Embodiments provide systems and methods for transfecting cells to produce a viral vector or other selected virus. One embodiment of a method for transfecting cells to produce a selected virus includes providing a first solution comprising plasmids or other extrachromosomal DNA encoding the virus and a second solution comprising a transfection agent; the two solutions kept separate. The two solutions are then mixed to produce a transfection solution (TS) to be delivered to a cell culture medium (CCM) for transfection of cells in the medium with the plasmid DNA encoding the virus wherein the mixing is initiated responsive to a trigger event. The TS is then incubated to form transfection complexes. Subsequently, the TS is delivered to the CCM to transfect the cells in the medium wherein a viral production parameter resulting from transfection is optimized by initiating mixing of the solutions responsive to the trigger event.

Provided herein is a powder comprising a live, attenuated virus, recombinant human serum albumin (rHSA), a sugar other than lactose, a sugar alcohol, a source of phosphate, a source of chloride, wherein the composition is substantially free of lactose, gelatin, antibiotic, and free amino acids. In exemplary aspects, the powder is a lyophilizate of a liquid composition. Related liquid compositions, methods of preparing an oncolytic virus for administration and methods of treating melanoma are also provided herein.

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding an immunomodulatory polypeptide (e.g., a pro-inflammatory cytokine such as a human IL-2 or IL-12 polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of cancer, such as lung cancer); and articles of manufacture or kits thereof.

The present invention relates to a combination comprising an oncolytic virus and an LTBR agonist. The LTBR agonist may be administered separately or may be encoded by the oncolytic virus. Such a combination is particularly useful for use in the treatment of a cancer.

Disclosed herein are high transducing replication defective herpes simplex virus (HSV) vectors, and methods of using the same.