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An HSV-2-based oncolytic virus deleted in the PK domain of the ICP10 gene is a potent inducer of apoptotic death in tumor cells

Gene Therapy volume 14, pages 1218–1225 (2007)Cite this article

Abstract

The N-terminus of the ICP10 gene of type 2 herpes simplex virus (HSV-2) encodes a serine/threonine protein kinase (PK) domain that facilitates HSV-2 replication by activating the Ras/MEK/MAPK mitogenic pathway and suppressing apoptosis. We recently demonstrated that deletion of this oncogenic PK domain converts it to a potent oncolytic agent. This mutant, which we have designated FusOn-H2, preferentially replicates in and thus lyses tumor cells in which the Ras signaling pathway is constitutively activated. Here we show that FusOn-H2 exerts strong ability in inducing apoptosis in different lines of human tumor cells and in esophageal tumors growing in mice. The apoptotic effect produced by FusOn-H2 was not restricted to infected cells but extended to uninfected bystander cells, thereby increasing the lethality of the virus. These results add a novel killing mechanism to those previously assigned to FusOn-H2, rendering it an attractive candidate for clinical trials.

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Acknowledgements

We thank Dr Mingrong Wang (Chinese Academy of Medical Sciences) for the gift of EC9706 cells and Dr Jonathan Prigge for critical reading of the manuscript. This project was supported in part by a grant from Department of Defense Ovarian Cancer Research Program (DAMD17-03-1-0434).

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Authors and Affiliations

  1. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA

    X Fu, L Tao & X Zhang

  2. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    X Fu, L Tao & X Zhang

  3. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA

    X Zhang

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Correspondence to X Zhang.

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Fu, X., Tao, L. & Zhang, X. An HSV-2-based oncolytic virus deleted in the PK domain of the ICP10 gene is a potent inducer of apoptotic death in tumor cells. Gene Ther 14, 1218–1225 (2007). https://doi.org/10.1038/sj.gt.3302971

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