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

Cancer Gene Therapy volume 9, pages 505–512 (2002)Cite this article

Abstract

The translation initiation factor eIF4E is elevated in most solid tumors resulting in translation of mRNAs 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.

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Acknowledgements

We extend our thanks to Dr Gloria Caldito for her guidance with the statistical analysis of this work. This work was supported by National Institutes of Health (NIH) Grant CA69148 and Grant BCTR0100512 from the Susan G Komen Foundation.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology and the Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, 71130-3932, Louisiana, USA

    Robert J DeFatta & Arrigo De Benedetti

  2. Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, 71130-3932, Louisiana, USA

    Robert P Chervenak

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  1. Robert J DeFatta
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  2. Robert P Chervenak
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  3. Arrigo De Benedetti
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Correspondence to Arrigo De Benedetti.

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DeFatta, R., Chervenak, R. & De Benedetti, A. A cancer gene therapy approach through translational control of a suicide gene. Cancer Gene Ther 9, 505–512 (2002). https://doi.org/10.1038/sj.cgt.7700469

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