A cancer gene therapy approach through translational control of a suicide gene

The translation initiation factor eIF4E is elevated in most solid tumors resulting in translation of mRN As that are normally repressed by their structured 5' untranslated region. We have introduced a translational repressor element in a vector (BK-UTK) designed to express herpes thymidine kinase(HTK). This and a control vector (BK-TK) were used to treat experimental tumors of a murine breast cancer line. Both vectors were equally effective in reducing subcutaneous tumors and lung metastases following ganciclovir administration. However, the BK-TK vector was found to be highly toxic, resulting in severe weight loss, degeneration of various organs, and early death of mice following systemic vector delivery, whereas the BK-UTK increased mean survival without toxicity.