Cell Genesys, Inc.

Calydon, Inc.

Other

Eric R Schuur

Daniel R Henderson

Henry G Lamparski

De-Chao Yu

Andrew S Little

De Chao Yu

Replication-competent adenovirus vectors specific for cells which allow a probasin transcriptional response element (PB-TRE) to function, such as cells which express the androgen receptor (AR), and methods of use of such viruses are provided. These viruses comprise an adenoviral gene under control of a transcriptional regulatory portion of a PB-TRE, which is in turn dependent upon AR expression. The gene can be, for example, a gene required for viral replication or the adenovirus death protein gene (ADP). The viruses can also comprise at least one additional adenoviral gene under control of at least one additional prostate-specific transcriptional response element, such as that controlling prostate-specific antigen expression (PSA-TRE). Thus, virus replication can be restricted to target cells exhibiting prostate-specific gene expression, particularly prostate carcinoma cells.

Adenovirus vectors specific for cells expressing androgen receptor and methods of use thereof

Replication competent adenoviral vectors specific for cells expressing alfa-fetoprotein (AFP) are provided. These replication-competetent adenoviral vectors comprise adenovirus genes essential for replication under the transcriptional control of an AFP-transcriptional regulatory element.

Adenovirus vectors specific for cells expressing alpha-fetoprotein and methods of use thereof

Compositions comprising host cell specific adenovirus vehicles are provided for transfecting target host cells. The compositions comprise replication competent adenovirus having an adenovirus gene essential for replication under transcriptional control of a cell type specific transcriptional response element (TRE) and polyethylene glycol (PEG) as a masking agent.

Compositions comprising tissue specific adenoviral vectors

Enhancers which preferentially increase the transcription of cis-linked coding sequences in prostate cells are provided. Methods of using DNA constructs comprising the enhancers to control transcription of heterologous polynucleotides are also provided. Delivery vehicles comprising the enhancers and methods of using the vehicles are also provided. Adenovirus vectors in which one or more genes are under transcriptional control of the enhancers of the invention are also provided. Further provided are methods of using the adenovirus vectors of the invention to confer selective cytotoxicity in mammalian cells.

Human glandular kallikrein enhancer, vectors comprising the enhancer and methods of use thereof

Host cell specific adenovirus vehicles are provided for transfecting target host cells. By providing for transcriptional initiating regulation dependent upon transcription factors that are only active in specific, limited cell types, virus replication will be restricted to the target cells. The modified adenovirus may be used as a vehicle for introducing new genetic capability, particularly associated with cytotoxicity for treating neoplasia.

Tissue specific adenoviral vectors

Adenovirus vectors replication specific for cells expressing &agr;-fetoprotein (AFP) and their methods of use are provided. By providing for a transcriptional initiating regulation dependent upon AFP expression, virus replication is restricted to target cells expressing AFP, particularly hepatocellular carcinoma cells. The adenovirus vectors can be used to detect and monitor samples for the presence of AFP-producing cells as well as to kill selectively malignant cells producing AFP.

Replication-competent adenovirus vectors specific for cells which allow a probasin transcriptional response element (PB-TRE) to function, such as cells which express the androgen receptor (AR), and methods of use of such viruses are provided. These viruses comprise and adenoviral gene under control of a transcription regulatory portion of a PB-TRE, which is in turn dependent upon AR expression. The gene can be, for example, a gene required for viral replication or the adenovirus death protein gene (ADP). The viruses can also comprise at least one additional adenoviral gene under control of at least one additional prostate-specific transcriptional response element, such as that controlling prostate-specific antigen expression (PSA-TRE). Thus, virus replication can be restricted to target cells exhibiting prostate-specific gene expression, particularly prostate carcinoma cells. An adenovirus of the present invention can further comprise a heterologus gene such as a reporter under transcriptional control of a PB-TRE. The adenovirus vectors can be used to detect and monitor samples for the presence of prostate cells as well as to selectively kill malignant cells producing prostate-specific gene products.

Replication-competent adenovirus vectors specific for cells which allows a probasin transcriptional response element (PB-TRE) to function, such as cells which express the androgen receptor (AR), and methods of use of such viruses are provided. These viruses comprise an adenoviral gene under control of a transcriptional regulatory portion of a PB-TRE, which is in turn dependent upon AR expression. The gene can be, for example, a gene required for viral replication or the adenovirus death protein gene (ADP). The viruses can also comprise at least one additional adenoviral gene under control of at least one additional prostate-specific transcriptional response element, such as that controlling prostate-specific antigen expression (PSA-TRE). Thus, virus replication can be restricted to target cells exhibiting prostate-specific gene expression, particularly prostate carcinoma cells. An adenovirus of the present invention can further comprise a heterologous gene such as a reporter under transcriptional control of a PB-TRE. The adenovirus vectors can be used to detect and monitor samples for the presence of prostate cells as well as to selectively kill malignant cells producing prostate-specific gene products.

Screening of compounds for activity toward inhibition of prostate cancer cell proliferation is provided. A cell line containing an expression construct comprising a transciptional initiation region of a prostate specific enhancer from a human glandular kallikrein (hKLK2) gene is employed which can be used in conventional equipment for determining activity of compounds, where the cell line uses a marker whose expression is responsive to therapeutically active compounds.

Prostate cancer drug screening using hKLK2 enhancer

Tissue specific and tumor growth supperssion by adenovirus comprising

Screening of compounds for activity toward inhibition of prostate cancer cell proliferation is provided. A cell line is employed which can be used in conventional equipment for determining activity of compounds, where the cell line uses a marker whose expression is responsive to therapeutically active compounds.

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Palo Alto, CA, United States of America

Eric R Schuur