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Analysis of HSV Oncolytic Virotherapy in Organotypic Cultures

  • Giulia FulciEmail author
  • Brent Passer
Protocol
Part of the Methods in Molecular Biology™ book series (MIMB, volume 542)

Summary

Tumor-selective replication-competent viral vectors, such as oncolytic herpes simplex virus (HSV) type I (HSV-1), represent an attractive strategy for tumor-based therapies because these viruses can replicate and spread in situ exhibiting cytopathic effects through direct oncolytic activity. These lytic viruses offer a distinct advantage over other forms of cancer therapies in that they are self-perpetuating and can spread not only in the tumor itself, but also to distant micrometastases. Translational studies aimed at identifying novel virotherapies for human cancers are incumbent upon the appropriate experimental models. While animal models are the preferred choice for efficacy studies of HSV virotherapy, we have developed a novel complementary approach toward assessing the effectiveness of oncolytic HSV therapy in both brain and prostate cancers. This experimental model takes advantage of previously published work in which human prostate cancer biopsies and rodent brain slices can be easily maintained ex vivo. The advantage of these systems is that the three-dimensional structure remains intact. Thus, all of the factors that may affect viral entry and replication, such as cell–cell and cell–matrix interactions, and interstitial fluid within this three-dimensional milieu remain preserved. Moreover, with respect to the brain, this system offers the advantage of direct access to brain cells, such as microglia and astrocytes, and circumvents the problems associated with the presence of the blood–brain barrier.

Keywords

Brain tumors HSV oncolytic virotherapy organotypic cultures prostate cancer 

Notes

Acknowledgments

This work was supported by a US Department of Defense (DOD) grant W81XWH-05-1-0367 to Brent J. Passer.

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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of NeurosurgeryBrain Tumor Research CenterCPZN-3800, BostonUSA

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