Disclosed herein are high transducing replication defective herpes simplex virus (HSV) vectors of McKrae strain.

An HSV vector with ICP27 under control of CXCR4 promoter and ICP34.5 under control of miRNA-124/143, wherein the vector has a deletion of one RL and one RS region of the viral genome. Within optional embodiments the mutation is a deletion containing the second copy of the ICP34.5 gene. These constructs provide increased safety without sacrificing efficacy. The HSV vector also incorporates a virus-expressed cytokine cassette encoding IL-12, IL-15/IL-15RA under the control of CMV promoter.

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.

Provided is a recombinant oncolytic herpes simplex virus type II (oHSV2) and its injection for treating central nervous system (CNS) tumor, such as a recurrent glioma.

Described herein is an oncolytic herpes simplex virus, G47hIL12A, which is G47 containing a cassette expressing a transgene, e.g., human IL-12, driven by a spontaneously arising genetically altered HCMV immediate-early (IE) enhancer/promoter. This virus has augmented (A) production of the transgene and increased virus replication while retaining safety. Also provided are methods of use thereof for treating cancer, e.g., glioblastoma (GBM) and triple-negative breast cancer (TNBC).

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.