Georgetown University

The General Hospital Corporation

Catherex, Inc.

Medigene, Inc.

Todo, Tomoki

Samuel D Rabkin

Robert L Martuza

Tomoki Todo

Paul Johnson

Toshihiro Mineta

Masahiro Toda

Hiroaki Wakimoto

Christopher Farrell

Cecile Zaupa

Ryuichi Kanai

Shin-ichi Miyatake

William Curry

Tomoki MD Todo

Robert Martuza

Masahiro c/o Inst Of Gene And Brain Science Toda

The invention provides viral vectors (e.g., herpes viral vectors) and methods of using these vectors to treat disease.

Viral vectors and their use in therapeutic methods

Eliciting a systemic antitumor immune response can be efficacious for a patient who presents with or who is at risk of developing multiple metastatic tumors of a given cell type. To this end a pharmaceutical composition is employed that comprises a defective HSV vector, preferably containing an expressible nucleotide sequence encoding at least one immune modulator.

Use of herpes vectors for tumor therapy

The invention, in some aspects, relates to the selective killing of cancer stem cells by oncolytic Herpes virus mediated oncolysis. In some aspects, the invention relates to methods for treating a subject having a cancer stem cell by administering to the subject an oncolytic Herpes virus. In other aspects, the invention provides methods for evaluating the efficacy of an oncolytic Herpes virus for killing cancer stem cells.

Use of oncolytic herpes viruses for killing cancer stem cells

Eliciting a systemic antitumor immune response, in a patient who presents with or who is at risk of developing multiple metastatic tumors of a given cell type, entails, in one embodiment, inoculating a tumor in the patient with a pharmaceutical composition consisting essentially of (A) a herpes simplex virus (HSV) that infects tumor cells but that does not spread in normal cells and (B) a pharmaceutically acceptable vehicle for the virus, such that an immune response is induced that is specific for the tumor cell type and that kills cells of the inoculated tumor and of a non-inoculated tumor. In another embodiment, the pharmaceutical composition also comprises a defective HSV vector which contains an expressible nucleotide sequence encoding at least one immune modulator. In another embodiment, the pharmaceutical composition contains a second HSV that infects tumor cells but that does not spread in normal cells. According to the latter approach, both the first HSV and the second HSV may have genomes that comprise, respectively, an expressible nucleotide sequence coding for at least one immune modulator. In another embodiment, the pharmaceutical composition comprises, in addition to a herpes simplex virus (HSV) that infects tumor cells but that does not spread in normal cells, a viral vector comprising at least one expressible nucleotide sequence coding for at least one immune modulator.

Method of stimulating an immune response (e.g., to treat cancer) include administering to a subject a composition including dendritic cells incubated with (i) oHSV-infected tumor cells or a composition derived therefrom, or (ii) tumor cells plus oHSV, as well as methods of preparing such compositions, are described.

Oncolytic herpes simplex virus immunotherapy in the treatment of brain cancer

A method for killing malignant brain tumor cells in vivo entails providing replication competent herpes simplex virus vectors to tumor cells. A replication competent herpes simplex virus vector, with defective expression of the &#x3b3;34.5 gene and the ribonucleotide reductase gene, specifically destroys tumor cells, is hypersensitive to anti-viral agents, and yet is not neurovirulent.

Replication-competent herpes simplex virus mediates destruction of neoplastic cells

A new gene therapy entails tumor treatment by introducing an expressible nucleotide sequence for a soluble costimulatory factor, thereby enhancing the response of T-cells to a tumor. In vivo expression of the soluble factor overcomes anergy or tolerance to tumor cells and activates T-cells that are infiltrating or surrounding the tumor. A pharmaceutical composition containing such a gene is effective in tumor suppression.

Use of soluble costimulatory factor for tumor immuno-gene therapy

A method for killing malignant brain tumor cells in vivo entails providing replication competent herpes simplex virus vectors to tumor cells. A replication competent herpes simplex virus vector, with defective expression of the &ggr;34.5 gene and the ribonucleotide reductase gene, specifically destroys tumor cells, is hypersensitive to anti-viral agents, and yet is not neurovirulent.

A method for killing malignant brain tumor cells in vivo entails providing replication competent herpes simplex virus vectors to tumor cells. A replication competent herpes simplex virus vector, with defective expression of the .gamma.34.5 gene and the ribonucleotide reductase gene, specifically destroys tumor cells, is hypersensitive to anti-viral agents, and yet is not neurovirulent.

Replication-competent Herpes simplex virus mediates destruction of

A method for killing tumor cells in vivo entails providing replication competent herpes simplex virus vectors to tumor cells. A replication competent herpes simplex virus vector, with an essential herpes simplex virus gene which is driven by a tumor-specific or cell-specific promoter that specifically destroys tumor cells and is not neurovirulent. Also, a method for producing an animal model, by ablating a specific cell type in vivo, entails providing replication competent herpes simplex virus vectors to the animal. Such a vector, with an essential herpes simplex virus gene driven by a cell- or tissue-specific promoter, specifically destroys the target cell type. This method of viral-mediated gene therapy employs cell-specific viral replication, where viral replication and associated cytotoxicity are limited to a specific cell-type by the regulated expression of an essential immediate-early (IE) viral gene product.

Growing community of inventors

Swampscott, MA, United States of America

Samuel D Rabkin