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A herpes simplex virus type 1 mutant deleted for γ34.5 and LAT kills glioma cells in vitro and is inhibited for in vivo reactivation

Cancer Gene Therapy volume 8, pages 269–277 (2001)Cite this article

Abstract

To create an oncolytic herpes simplex virus type 1 (HSV-1) that is inhibited for reactivation, we constructed a novel herpes recombinant virus with deletions in the γ34.5 and LAT genes. The LAT gene was replaced by the gene for green fluorescent protein, thereby allowing viral infection to be followed. This virus, designated DM33, is effective in killing primary and established human glioma cell lines in culture. DM33 is considerably less virulent following intracerebral inoculation of HSV-susceptible BALB/c mice than the wild-type HSV-1 strain McKrae. The safety of this virus is further supported by the retention of its sensitivity to ganciclovir and its relatively limited toxicity against cultured human neuronal cells, astrocytes, and endothelial cells. The ability of DM33 to spontaneously reactivate was tested in a rabbit ocular infection model that accurately depicts human herpes infection and reactivation. Following ocular infection of rabbits, spontaneous reactivation was detected in 83% (15/18) of the eyes infected with wild-type McKrae. In contrast, none of the eyes infected with DM33 had detectable reactivation. The efficacy of this virus in cultured human glioma cell lines, its safety, confirmed by its inability to reactivate, and its attenuated neurovirulence make DM33 a promising oncolytic agent for tumor therapy. Cancer Gene Therapy (2001) 8, 269–277

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Authors and Affiliations

  1. The Maxine-Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, 90048, California

    Ken Samoto, Moneeb Ehtesham, Yunhui Liu, Keith L Black & John S Yu

  2. Department of Neurosurgery, University of California at Irvine, Irvine, California

    Ken Samoto, Moneeb Ehtesham, Yunhui Liu, Keith L Black & John S Yu

  3. Ophthalmology Research Laboratories, Cedars-Sinai Medical Center, Burns and Allen Research Institute, Los Angeles, 90048, California

    Guey-Chuen Perng, Steven L Wechsler & Anthony B Nesburn

  4. Department of Ophthalmology, University of California at Los Angeles, Los Angeles, California

    Guey-Chuen Perng, Steven L Wechsler & Anthony B Nesburn

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  1. Ken Samoto
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  8. John S Yu
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Correspondence to John S Yu.

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Samoto, K., Perng, GC., Ehtesham, M. et al. A herpes simplex virus type 1 mutant deleted for γ34.5 and LAT kills glioma cells in vitro and is inhibited for in vivo reactivation. Cancer Gene Ther 8, 269–277 (2001). https://doi.org/10.1038/sj.cgt.7700306

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