Abstract: Chimeric viruses having a vesicular stomatitis virus (VSV) background where the VSV G protein is supplemented or replaced with an alphavirus glycoprotein(s), or a functional fragment(s) thereof, are provided. A preferred alphavirus is Chikungunya virus. In particular embodiments, the glycoprotein(s) is or includes E3, E2, K6, and E1 proteins of an alphavirus, preferably Chikungunya virus. Methods of using the chimeric viruses for treatment of cancers, particularly brain cancers and metastasis thereof are also provided. In some embodiments, the chimeric viruses retain superior oncolytic activity to infect and destroy cancer cells selectively, such as glioblastoma and intracranial melanoma metastases. In some embodiments, the chimeric viruses have reduced toxicity to e.g., heathy cells relative to a control such as the parent VSV with the VSV G protein.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: Oncolytic VSV viruses have been developed as a strategy for combating cancer. The present invention includes mutant VSV that have one or more mutations in the nucleic acid sequence encoding the viral genome that increase the oncolytic potential of the virus. Pharmaceutical compositions including oncolytic virus disclosed herein are also provided. Pharmaceutical compositions containing virus and one or more excipients may be for systemic or local administration. Methods of administering an effective amount of the compositions for treating cancer are disclosed. Preferred routes of administration include intratumeral and intravenous injection, and intranasal delivery. Administration of the disclosed compositions containing oncolytic viruses may be coupled with surgical, radiologic, other therapeutic approaches to treatment of cancer. Methods of manufacturing mutant VSV viruses exhibiting desired properties include applying selective pressure, and through directed or random mutagenesis.

Abstract: Compositions including attenuated oncolytic viruses and methods of their use for the treatment of cancer are disclosed. Some attenuated virus exhibit potential as tumor therapies by exhibiting characteristics such as high selectivity, infectivity, cytotoxicity, or replication index for tumor cells, and/or low infectivity, cytotoxicity, or replication index for normal cells. In preferred embodiments, the ratio of replication of virus in normal cells:tumor cells is about 1:100 or greater. Preferred viruses have two or more mechanisms of attenuation including insertion of a transgene such as GFP or an interferon, preferably at position 1 of the viral genome. The compositions can be administered to subjects having tumors, in an effective amount to delay or inhibit the growth of a tumor, reduce the growth or size of the tumor, and/or inhibit or reduce metastasis of the tumor. Methods for manufacturing viruses and methods of testing their oncolytic potential are also disclosed.

Abstract: Methods for protecting the brain and other tissues from virus-associated toxicity are provided. Patients are treated with a first immunizing virus prior to administration of a second, therapeutic cytolytic virus. The immunizing virus is preferably administered peripherally, and initiates an adaptive immune response that is sufficient to reduce or prevent the cytovirulence and inflammation caused by the therapeutic virus. The immunizing virus is administered one or more times, preferably at least twice, before administration of the therapeutic virus. The therapeutic virus can be the same virus as the immunizing virus, or a mutant or variant thereof. Preferably the therapeutic virus is an attenuated virus with reduced virulence compared to the immunizing virus.

Abstract: Oncolytic VSV viruses have been developed as a strategy for combating cancer. The present invention includes mutant VSV that have one or more mutations in the nucleic acid sequence encoding the viral genome that increase the oncolytic potential of the virus. Pharmaceutical compositions including oncolytic virus disclosed herein are also provided. Pharmaceutical compositions containing virus and one or more excipients may be for systemic or local administration. Methods of administering an effective amount of the compositions for treating cancer are disclosed. Preferred routes of administration include intratumeral and intravenous injection, and intranasal delivery. Administration of the disclosed compositions containing oncolytic viruses may be coupled with surgical, radiologic, other therapeutic approaches to treatment of cancer. Methods of manufacturing mutant VSV viruses exhibiting desired properties include applying selective pressure, and through directed or random mutagenesis.

Abstract: A method for phase shifting the circadian pacemaker or treating seasonal affective disorder in a subject is disclosed. The method includes exposing the subject's eye region to a given-intensity light flash having a flash duration of between about 1-500 msec, at a periodicity of at least about one flash per minute, over a selected time period effective, were the subject exposed to a continuous light pulse of the same intensity for this period, to phase shift the circadian pacemaker or treat the seasonal affective disorder in the subject. Also disclosed is a device for practicing the method.