Abstract: A novel gene therapy for cancer has been discovered, which unlike most prior appraches, does not require specific knowledge of the cancer cells, but instead targets a general characteristic that distinguishes cancer cells from normal cells, i.e., elevated eIF4E expression. The expression of a toxin or conditional toxin such as HTK is translationally repressed in normal cells by placing a complex 5′ UTR in front of its reading frame. In prototype experiments, this HTK mRNA, a transcriptional product of the BK-UTK vector, was translationally regulated so as to largely inhibit its production in normal murine and human cells, while cancer cells efficiently translated the protein, which a resulting increased sensitivity to GCV. Synthesis of the HTK protein from the BK-UTK vector (containing the 5′ UTR of Fibroblast growth factor −2 (“FGF-2”) readily occurred in a panel of murine and human breast carcinoma lines, but not in normal cell lines.
Type:
Grant
Filed:
July 26, 2001
Date of Patent:
July 6, 2004
Assignee:
Board of Supervisors of La. State Un. & Agricultural and
Mechanical College