The present invention relates to compositions and methods for enhancing
the oncolytic activity of replication-competent, target cell-specific
adenovirus vectors by modification of the E1A gene product. The target
cell-specific replication-competent adenovirus vectors comprise a chimera
of an adenovirus gene essential for replication, preferably an early
gene, and the Androgen receptor (or a portion thereof) under the
transcriptional control of a cell type-specific transcriptional
regulatory element (TRE). By providing for cell type-specific
transcription through the use of one or more cell type-specific TREs, the
adenovirus vectors effect prostate-specific cytotoxicity due to selective
replication.