© 2003 by Oxford University Press
Journal of the National Cancer Institute, Vol. 95, No. 9, 633,
May 7, 2003
© 2003 Oxford University Press
Press Release
Modified Adenovirus Offers New Approach to Treating Aggressive Brain Tumors
jncimedia{at}oupjournals.org
Researchers have created a modified adenovirus that more readily attaches to brain tumor cells, thereby infecting them and causing antitumor effects. This modified adenovirus may potentially offer a more effective approach to treating aggressive brain tumors, according to a new study in the May 7 issue of the Journal of the National Cancer Institute.
Previous research has shown that infection of gliomas, a type of brain tumor, with an adenovirus called Delta-24 inhibits tumor growth. The ability of Delta-24 to infect tumor cells depends on its ability to anchor to coxsackie-adenovirus receptors (CARs); however, tumor cells express CAR at low levels, making virus-based therapy difficult. In fact, Delta-24 has shown limited success as a treatment for gliomas.
Because tumor infection by adenoviruses can also be mediated by cell-surface integrins, Juan Fueyo, M.D., of the University of Texas M. D. Anderson Cancer Center in Houston, and his colleagues modified Delta-24 to bypass CAR and anchor directly to these integrins. They hypothesized that this modified adenovirus, called Delta-24-RGD, would be more infective than Delta-24 in gliomas.
Compared with Delta-24, Delta-24-RGD infected tumor cells 6 times better, replicated more efficiently, was more cytopathic (causing cell death), and was associated with increased survival in a mouse model of human glioma. Sixty percent of mice treated with Delta-24-RGD survived more than 4 months, compared with only 15% of mice treated with the unmodified adenovirus.
The authors point out that modification of Delta-24 did not affect the ability of the adenovirus to bind to CAR, nor did the modification alter the toxicity of the Delta-24 adenovirus in cancer cells. They conclude that Delta-24-RGD may have the potential of being an effective agent in the treatment of gliomas.
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Contact: Laura Sussman, University of Texas M. D. Anderson Cancer Center, 713-792-0655; fax: 713-792-0655, lsussman{at}mdanderson.org.
Fueyo J, Alemany R, Gomez-Manzano C, Fuller GN, Khan A, Conrad CA, et al. Preclinical characterization of the antiglioma activity of a tropism-enhanced adenovirus targeted to the retinoblastoma pathway. J Natl Cancer Inst 2003;95:652–60.
Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage.
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