A recombinant herpes virus showing high antitumor activity is provided. In particular, a recombinant herpes simplex virus that expresses an ICP6 gene under control of a tumor-specific promoter or tissue-specific promoter on the genome of the virus is provided.

Malignant tumors that are resistant to conventional therapies represent significant therapeutic challenges. An embodiment of the present invention provides a regulatable fusogenic oncolytic herpes simplex virus-1 that is more effective at selective killing target cells, such as tumor cells. In various embodiments presented herein, the oncolytic virus described herein is suitable for treatment of solid tumors, as well as other cancers.

The present invention refers to a vector system, usable as a platform vector and suitable for the production of transgenic viruses of the subfamily Alphaherpesvirinae. Such transgenic viruses can be used as vaccine or as oncolytic virus or in gene therapy. The platform vector of the present invention is a vector system allowing a simplified search for and generation and production of viruses with a modified and increased functionality. The present invention refers also to the use of the platform vector as a vector system for the generation and the production of transgenic viruses, methods for the production of a transgenic virus, using the vector system of the present invention and viruses obtained by such methods.

The present disclosure relates to cellular compositions that are modified to introduce an oncolytic virus. Such compositions may be used to treat cancer by delivering oncolytic virus to cancer cells.

Recombinant oncolytic viruses that produce and secrete novel immunomodulatory fusion proteins are described. The fusion proteins encode a single chain variable fragment antibody (ScFv) that specifically binds PD-1 OR PD-L1 fused via an antibody Fc region to the ectodomain of the TGFβ receptor II (TGFβRII.sub.ecto). The immunomodulatory fusion proteins have dual function: blocking inhibitory pathways mediated by PD-1/PD-L1 and blocking the immune-dampening activity of TGFβ. In addition, dual gene oncolytic herpes simplex viruses (HSVs) are provided that include, in addition to a gene encoding an ScFv-Fc-TGFβRII.sub.ecto fusion protein, a gene encoding IL12, a T cell stimulatory factor.

In certain aspects, the disclosure relates to a virus engineered to comprise one or more polynucleotides that promote thanotransmission by a target cell. Thanotransmission is communication between cells that is a result of activation of a cell turnover pathway in a target cell, which signals a responding cell to undergo a biological response. Methods of promoting thanotransmission by a target cell, methods of promoting an immune response in a subject, and methods of treating cancer in a subject are also disclosed.

Disclosed are novel modified viruses comprising recombinant PTEN-Long and methods of using the same for treating cancer.

Provided herein is a replication-defective oncolytic herpes simplex virus 1 (HSV-1) recombinant virus, comprising within its genome: a coding sequence encoding a fusion protein.

The present invention relates to an oncolytic virus which is, or is derived from, a clinical isolate which has been selected by comparing the abilities of a panel of three or more clinical isolates of the same viral species to kill tumor cells of two or more tumor cell lines in vitro and selecting a clinical isolate which is capable of killing cells of two or more tumor cell lines more rapidly and/or at a lower dose in vitro than one or more of the other clinical isolates in the panel.

Provided herein are compositions and methods for vaccination and research applications. In particular, provided herein are non-neuroinvasive herpesviruses and alpha herpesviruses and uses thereof.