Boehringer Ingelheim International Gmbh

Yale University

Viratherapeutics Gmbh

Guido Wollmann

Klaus Erb

Anthony N Van Den Pol

Philipp Mueller

Patrik Erlmann

John Edward Park

Tobias Friederike Nolden

The present invention relates to the field of oncolytic viruses and in particular to a recombinant rhabdovirus, such as vesicular stomatitis virus encoding in its genome for a CCL21 protein. The invention is further directed to the use of the recombinant virus in the treatment of cancer, and also to methods for producing such viruses.

Recombinant rhabdovirus encoding for CCL21

The present invention relates to the field of oncolytic viruses and in particular to a recombinant rhabdovirus, such as vesicular stomatitis virus encoding in its genome for a CD80 extracellular domain Fc-fusion protein. The invention is further directed to the use of the recombinant virus in the treatment of cancer, and also to methods for producing such viruses.

Recombinant rhabdovirus encoding for a CD80 extracellular domain Fc-fusion protein

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.

Chimeric VSV virus compositions and methods of use thereof for treatment of cancer

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.

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Innsbruck, Austria

Guido Wollmann