Embodiments of the invention include compositions and methods related to non-VSV rhabdoviruses and their use as anti-cancer therapeutics. Such rhabdoviruses possess tumor cell killing properties in vitro and in vivo.

Provided is a modified matrix protein of a vesicular stomatitis virus, wherein the protein has amino acid substitutions at position 21, position 51, position 111 and position 221. Further provided are an attenuated strain of the vesicular stomatitis virus producing the modified matrix protein, a composition containing the attenuated strain, and uses thereof in preparing a drug for killing abnormally proliferating cells, inducing and promoting antitumor immune response, or eliminating immunosuppression in a microenvironment of a tumor tissue.

This document relates to methods and materials involved in treating cancer. For example, methods and materials for using one or more oncolytic viruses (OVs) in combination with an adoptive cell therapy (e.g., a chimeric antigen receptor T cell therapy) to alter one or more functions of a T cell and/or to enhance T cell expansion to treat cancer in a mammal (e.g., a human) are provided.

There is described a kit for use in inducing an immune response in a mammal, the kit includes: a first virus that expresses MAGEA3, Human Papilloma Virus E6/E7 fusion protein, human Six-Transmembrane Epithelial Antigen of the Prostate protein, or Cancer Testis Antigen 1, or a variant thereof as an antigenic protein and that is formulated to generate an immunity to the protein or variant thereof in the mammal. The kit also includes a Maraba MG1 virus encoding the same antigen, or a variant of the same antigen. The Maraba MG1 virus is formulated to induce the immune response in the mammal. The first virus is immunologically distinct from the Maraba MG1 virus.

Methods of treating cancer including administering to a subject with cancer a pharmaceutical composition including an effective amount of a chimeric VSV virus are disclosed. The chimeric viruses are based on a VSV background where the VSV G protein is replaced with one or more heterologous viral glycoproteins. In the most preferred embodiment, the VSV G protein is replaced with the glycoprotein from Lassa virus or a functional fragment thereof. The resulting chimeric virus is an oncolytic virus that is attenuated and safe in the brain, yet still retains sufficient oncolytic activity to infect and destroy cancer cells such glioblastoma, and to generate an immune response against infected cancer cells. Methods of using chimeric viruses as a platform for immunization against other pathogenic microbes are also provided.

The present disclosure provides a miRNA hairpin that, when processed by a virus-infected cell, increases the therapeutic effectiveness of the virus. The present disclosure also provides a virus encoding such a miRNA hairpin. The present disclosure also provides pre-miRNAs that, when processed by a virus-infected cell, increase extracellular vesicle secretion of the encoded miRNA hairpin by the virus-infected cell.

The present invention relates to recombinant oncolytic viruses comprising a vesicular stomatitis virus (VSV), wherein the glycoprotein (G protein) of VSV is deleted; and which comprises a modified fusion protein (F protein) of Newcastle disease virus (NDV); and the hemagglutinin neuraminidase (HN) protein of NDV. The present invention further relates to nucleic acids encoding for the recombinant oncolytic virus and vectors comprising the nucleic acids. The present invention further relates to pharmaceutical compositions comprising the rVSV of the invention, the nucleic acid or the vector, further to uses as gene delivery tool and/or for tumor detection. The present invention further relates to the recombinant oncolytic vesicular stomatitis virus (VSV) for use in medicine, in particular for the diagnosis, prevention and/or treatment of cancer.

The present disclosure relates, in general, to recombinant viral vectors that stimulate STING (STimulator of INterferon Genes) activity and increase activity of immune cells.

This document provides methods and materials related to vesicular stomatitis viruses. For example, replication-competent vesicular stomatitis viruses, nucleic acid molecules encoding replication-competent vesicular stomatitis viruses, methods for making replication-competent vesicular stomatitis viruses, and methods for using replication-competent vesicular stomatitis viruses to treat cancer or infectious diseases are provided.

This document provides methods and materials related to treating cancer. For example, methods and materials for using nucleic acid libraries to treat cancer are provided.