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.

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.

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.

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 invention provides an in vivo individualized systemic immunotherapeutic method and device. The method includes, in a non-sequential manner: (1) increasing release amount of tumor antigens at a tumor site; (2) at the tumor site, increasing level of proteins capable of adhering to and/or wrapping the tumor antigens; (3) at the tumor site, increasing level of dedicated antigen-presenting cells involved in immunity, and establishing, between the dedicated antigen-presenting cells and immune effector cells, a close connection capable of activating the immune effector cells; and (4) at the tumor site, increasing level and improving function of the immune effector cells. The steps (1)-(4) each reaches a maximum value at a respective time which overlaps with each other maximally, as well as at a respective site which overlaps with each other maximally. The invention combines oncolytic therapy and immunotherapy, in individualized systemic immunotherapy, and provides significantly improved therapeutic effect.

The invention provides an in vivo individualized systemic immunotherapeutic method and device. The method includes, in a non-sequential manner: (1) increasing release amount of tumor antigens at a tumor site; (2) at the tumor site, increasing level of proteins capable of adhering to and/or wrapping the tumor antigens; (3) at the tumor site, increasing level of dedicated antigen-presenting cells involved in immunity, and establishing, between the dedicated antigen-presenting cells and immune effector cells, a close connection capable of activating the immune effector cells; and (4) at the tumor site, increasing level and improving function of the immune effector cells. The steps (1)-(4) each reaches a maximum value at a respective time which overlaps with each other maximally, as well as at a respective site which overlaps with each other maximally. The invention combines oncolytic therapy and immunotherapy, in individualized systemic immunotherapy, and provides significantly improved therapeutic effect.