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US 2004/0110716 A1Published application
Cancer gene therapy based on translational control of a suicide gene
OwnerArrigo DeBenedetti, Robert J. DeFattainventors
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OwnerArrigo DeBenedetti, Robert J. DeFattainventors
Estimating the term…
A novel gene therapy for cancer has been discovered, which unlike most prior approaches, 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. Subcutaneous tumors and experimental lung metastases of the breast carcinoma line MM2MT in BALB/c mice were greatly reduced by transfection with the BK-UTK vector, followed by GCV administration. Both the BK-UTK and the BK-TK (control) vectors were effective in reducing lung metastasis following systemic delivery of the vectors and subsequent GCV administration. However, the BK-TK vector was highly toxic to mice while little to no toxicity was seen in mice treated with the BK-UTK vector.
A method for selectively expressing a toxin within a cell comprising administering to the cell a DNA sequence comprising a promoter operatively linked to a transcription sequence;
A method for selectively expressing a toxin within a cell comprising administering to the cell a messenger RNA sequence that comprises a translatable sequence encoding a toxin, and an untranslated sequence;
A method of treatment for cancer in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a DNA sequence comprising a promoter operatively linked to a transcription sequence;
A method of treatment for cancer in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a messenger RNA sequence that comprises a translatable sequence encoding a toxin, and an untranslated sequence;
Dependencies are inferred from the claim text.