Turnstone Limited Partnership

Children's Hospital Of Eastern Ontario Research Institute Inc.

Ottawa Hospital Research Institute

Wellstat Biologics Corporation

University Of Ottawa

Mcmaster University

David F Stojdl

John Cameron Bell

Brian D Lichty

Harold L Atkins

Christopher John Brown

Robert Michael Lorence

Michael Scot Roberts

Ricardo M Marius

Shane B Knowles

Nahum Sonenberg

Conrad J Heilman, Jr

Jonathan Pol

Earl G Brown

The present disclosure concerns an oncolytic virus for the treatment of cancer, such as in brain cancer, for example glioblastoma. The oncolytic virus may exhibit reduced levels of neurotoxicity. The oncolytic virus may be an isolated viral particle capable of producing a cDNA polynucleotide that includes a sequence according to SEQ ID NO: 1 when the virus is in a host cell. The oncolytic virus may be an isolated viral particle that includes an RNA polynuclotide that includes a sequence according to SEQ ID NO: 2. The oncolytic virus may be an isolated viral particle having a genome that includes open reading frames that encode: proteins having sequences comprising SEQ ID NOs: 3, 4, 5, 6 and 7; or variants thereof.

Compositions and methods for glioblastoma treatment

The present disclosure concerns an oncolytic virus for the treatment of cancer, such as in brain cancer, for example glioblastoma. The oncolytic virus may exhibit reduced levels of neurotoxicity. The oncolytic virus may be an isolated viral particle capable of producing a cDNA polynucleotide that includes a sequence according to SEQ ID NO: 1 when the virus is in a host cell. The oncolytic virus may be an isolated viral particle that includes an RNA polynucleotide that includes a sequence according to SEQ ID NO: 2. The oncolytic virus may be an isolated viral particle having a genome that includes open reading frames that encode: proteins having sequences comprising SEQ ID NOs: 3, 4, 5, 6 and 7; or variants thereof.

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.

Vaccine composition

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

Oncolytic rhabdovirus

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.

The present invention is directed to a method of reducing the viability of a tumor cell involving administering a virus that is not a common human pathogen to the tumor cell. Preferably, the virus exhibits differential susceptibility, in that normal cells are not affected by the virus. This differential susceptibility is more pronounced in the presence of interferon. The tumor cell is characterized by having low levels, or no, PKR activity, or as being PKR&#x2212;/&#x2212;, STAT1&#x2212;/&#x2212; or both PKR&#x2212;/&#x2212; and STAT1&#x2212;/&#x2212;. The virus is selected from the group consisting of Rhabdovirus and picornavirus, and preferably is vesicular stomatitis virus (VSV) or a derivative thereof.

Oncolytic virus

The present invention provides mutant viruses with a decreased ability to block nuclear transport of mRNA or protein in an infected cell which are attenuated in vivo. The mutant viruses of the present invention may also be capable of triggering the anti-viral systems of normal host cells while remaining sensitive to the effects of these systems. The present invention further provides for the use of the mutant viruses in a range of applications including, but not limited to, as therapeutics for the treatment of cancer and infections, as vaccines and adjuvants, as viral vectors, and as oncolytic and cytolytic agents for the selective lysis of malignant or infected cells.

Mutant vesicular stomatitis viruses and uses thereof

The subject invention relates to viruses that are able to purge (reduce or eliminate) undesirable cells in a mixture of cells. Undesirable cells can include neoplastic cells, cells mediating graft-versus host diseases, and autoimmune cells. The subject invention also relates to the purging of undesirable cells from bone marrow or peripheral blood cell harvests in the treatment of mammals including cancer patients, transplant recipients, and patients with autoimmune disease.

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Ottawa, Canada

David F Stojdl