Enhancement of Adenoviral Oncolytic Activity by Modification of the E1A Gene Product

Unmet Need: Prostate cancer is a multi-focal disease with clones of androgen-sensitive and androgen-refractory cells, yet, the specific role androgen receptors (ARs) may play in prostate cancer in not clear. There remains an unmet need for new specific treatment modalities that selectively target diseased tissue and are capable of effectively killing both androgen-responsive and androgen-refractory cancer cells. Disclosed herein is a target cell-specific replication-competent adenovirus vector that selectively replicates in prostate cells, thereby providing tissue-specific cytotoxicity. Advantages include:

• Tissue-specific replication conditional adenovirus vector comprising a prostate-specific transcriptional regulatory element and an E1A/AR chimeric protein
• Exerts prostate cell-specific cytotoxicity for targeted cancer therapy
• Enables treatment of cell-specific replication-competent cells

 
Technical Details: 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. 
 
Patent Status: Granted US Patent 7,662,795

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