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

Abstract

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. 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.

1 - 38 . (canceled) 
     
     
         39 . A method of treating prostate cancer in an individual, comprising the step of administering to the individual an effective amount of an adenovirus vector comprising an adenovirus gene essential for replication under transcriptional control of a probasin transcriptional regulatory element (PB-TRE). 
     
     
         40 . The method of  claim 39 , wherein the adenovirus vector further comprises an adenovirus death protein gene (ADP). 
     
     
         41 . The method of  claim 39 , wherein the PB-TRE comprises an enhancer from a probasin gene. 
     
     
         42 . The method of  claim 39 , wherein the PB-TRE comprises a promoter from a probasin gene. 
     
     
         43 . The method of  claim 39 , wherein the PB-TRE comprises a promoter from a probasin gene and an enhancer from a probasin gene. 
     
     
         44 . The method of  claim 39 , wherein the PB-TRE comprises at least one androgen response element (ARE). 
     
     
         45 . The method of  claim 39 , wherein the PB-TRE comprises androgen response elements 1 and 2 (ARE-1 and ARE-2) of a probasin gene. 
     
     
         46 . The method of  claim 39 , wherein the PB-TRE comprises nucleotides about 141 to about 454 of SEQ ID NO:1. 
     
     
         47 . The method of  claim 39 , wherein the PB-TRE comprises nucleotides about 191 to about 204 or about 286 to about 310 of SEQ ID NO:1. 
     
     
         48 . The method of  claim 39 , wherein the PB-TRE comprises nucleotides about 191 to about 204 and about 286 to about 310 of SEQ ID NO:1. 
     
     
         49 . The method of  claim 39 , wherein the PB-TRE comprises SEQ ID NO:1. 
     
     
         50 . The method of  claim 39 , wherein the adenovirus vector further comprises at least one additional adenovirus gene under transcriptional control of at least one additional prostate-specific transcriptional regulatory element. 
     
     
         51 . The method of  claim 50 , wherein the at least one additional prostate-specific transcriptional regulatory element is selected from the group consisting of a PB-TRE and a prostate-specific antigen (PSA) TRE. 
     
     
         52 . The method of  claim 39 , wherein the adenovirus gene is selected from the group consisting of an adenovirus early gene and an adenovirus late gene. 
     
     
         53 . The method of  claim 52 , wherein the adenovirus early gene is selected from the group consisting of E1A and E1B. 
     
     
         54 . The method of  claim 39 , wherein the adenovirus vector further comprises a heterologous gene under transcriptional control of a probasin transcriptional regulatory element (PB-TRE).