Cedars-sinai Medical Center

Steven L Wechsler

Anthony B Nesburn

Homayon Ghiasi

Keith L Black

John S Yu

Guey-Chuen Perng

Homayan Ghiasi

Disclosed is an HSV-1-derived vector containing a DNA having a functional LAT promoter, or operative fragment thereof, a deletion in both copies of the HSV-1 LAT gene, and a deletion in both copies of the HSV-1 ICP34.5 gene. The HSV-1-derived vectors are non-neurovirulent and do not spontaneously reactivate from latency, and they optionally contain a functional HSV thymidine kinase gene, which can enhance the effectiveness against cancer of drug treatment with gancyclovir or acyclovir. Alternatively, the HSV-1-derived vectors contain at least one transcriptional unit of a LAT promoter sequence operatively linked to a nucleic acid encoding a preselected protein. In some embodiments, the preselected protein is a nucleotide sequence encoding a polypeptide toxic for cells expressing the vector, for example, human interferon-&#x3b3;. Also, disclosed are kits for expressing in a mammalian cell a gene encoding a preselected protein, and mammalian cells containing the HSV-derived vectors.

Herpes simplex virus type 1 (HSV-1)-derived vector for selectively inhibiting malignant cells and for expressing desired traits in malignant and non-malignant mammalian cells

Disclosed is a method of selectively inhibiting the growth of malignant cells in mammals, including humans. The method selectively inhibits the growth of malignant cells of all varieties, and is particularly useful in treating brain tumors and other malignancies of the central nervous system. The method employs HSV-1-derived vectors containing a DNA having a deletion in both copies of the LAT gene and both copies of the ICP34.5 gene of HSV-1. The vectors are delivered to malignant cells either in vivo or in vitro, in accordance with the method. The HSV-1-derived expression vectors are non-neurovirulent and do not spontaneously reactivate from latency, and they optionally contain a functional HSV thymidine kinase gene, which can enhance the effectiveness against cancer of drug treatment with gancyclovir or acyclovir. Alternatively, the HSV-1-derived vectors contain at least one transcriptional unit of a LAT promoter sequence operatively linked to a nucleic acid having a nucleotide sequence encoding a polypeptide toxic for cells expressing the vector, for example, human interferon-&ggr;. A method of expressing in a mammalian cell a gene encoding a preselected protein, a method of treating a genetic defect, and a method of detecting an HSV-1 expressing cell also employ vectors of the present invention that contain at least one transcriptional unit of a constitutive LAT promoter operatively linked to and controlling the transcription of a gene encoding a preselected protein. Also, disclosed are kits for expressing in a mammalian cell a gene encoding a preselected protein, useful for practicing the methods, and mammalian cells containing the HSV-derived vectors.

HERPES SIMPLEX VIRUS TYPE 1 (HSV-1)-DERIVED VECTOR FOR SELECTIVELY INHIBITING MALIGNANT CELLS AND METHODS FOR ITS USE TO TREAT CANCERS AND TO EXPRESS DESIRED TRAITS IN MALIGNANT AND NON-MALIGNANT MAMMALIAN CELLS

The present invention relates to the field of infectious diseases and ophthalmology. More particularly, the invention relates to compositions and methods for vaccination against Herpes Simplex Virus which rely on preparations comprising a mixture of five, six, or seven HSV glycoproteins selected from the group consisting of gB, gC, gD, gE, gG, gH, and gI.

Pharmaceutical composition of herpes simplex virus typ-1 (HSV-1) glycoproteins

Pharmaceutical compsition of herpes simplex virus type-1 (HSV-1),

Immunotherapy for the treatment of Herpes Simplex Virus eye infections is disclosed. The invention involves a local therapeutic or prophylactic vaccine for the eye, comprising one or more recombinant HSV-1 glycoproteins or proteins, specifically gB and gD, in combination with at least one adjuvant to reduce the incidence of primary HSV-1 infection and/or decrease spontaneous HSV-1 ocular shedding which in turn, controls recurrent corneal disease.

Immunotherapy for recurrent HSV infections

A process for obtaining Herpes Simplex virus type 1 (HSV-1) glycoprotein I (gI) from cells which have been infected or transformed with a recombinant Baculovirus is disclosed. The gI produced is then isolated and purified for use in immunotherapy against HSV infections.

Process for the expression of herpes simplex virus type 1 glycoprotein I

A process for obtaining Herpes Simplex virus type 1 (HSV-1) glycoprotein E (gE) from cells which have been infected or transformed with a recombinant Baculovirus is disclosed. The gE produced is then isolated and purified for use in immunotherapy against HSV infections.

Growing community of inventors

Westlake Village, CA, United States of America

Steven L Wechsler