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Analysis of genetically engineered oncolytic herpes simplex viruses in human prostate cancer organotypic cultures

Gene Therapy volume 16, pages 1477–1482 (2009)Cite this article

Abstract

Oncolytic herpes simplex viruses type 1 (oHSVs) such as G47Δ and G207 are genetically engineered for selective replication competence in cancer cells. Several factors can influence the overall effectiveness of oHSV tropism, including HSV-1 receptor expression, extracellular matrix milieu and cellular permissiveness. We have taken advantage of human prostate organ cultures derived from radical prostatectomies to investigate oHSV tropism. In this study, we show that both G47Δ and G207 specifically replicate in epithelial cells of the prostatic glands but not in the surrounding stroma. In contrast, both the epithelial and stromal cell compartments were readily infected by wild-type HSV-1. Analysis of oHSV replication in prostate surgical specimens 3 days post infection showed that G47Δ generated ∼30-fold more viral progeny than did G207. This correlated with the enhanced expression of G47Δ-derived glycoprotein gB protein levels as compared with G207. In benign prostate tissues, G207 and G47Δ titers were notably reduced, whereas strain F titers were maintained at similar levels compared with prostate cancer specimens. Overall, our results show that these oncolytic herpes vectors show both target specificity and replication competence in human prostate cancer specimens and point to the utility of using human prostate organ cultures in assessing oHSV tropism and cellular specificity.

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Acknowledgements

We would like to thank Drs T. Kasic and A. Viola (University of Padova; Padova, Italy) for their helpful advice on setting up conditions for prostate organ cultures. We are grateful to Dr CA Krummenacher (University of Pennsylvania School of Dental Medicine; Philadelphia, PA, USA) for supplying the R166 antibody. We thank Dr G Fulci (Massachusetts General Hospital) for expertise on immunohistochemistry and Ms. Melissa Marinelli for laboratory assistance. RLM an SDR are consultants to MediGene Ag, which has a license from Georgetown University for G207. Support for this study was in part obtained from a grant to RLM (RO1 CA102139).

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Authors and Affiliations

  1. Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    B J Passer, S D Rabkin & R L Martuza

  2. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    C-l Wu & S Wu

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  1. B J Passer
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Correspondence to B J Passer.

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Passer, B., Wu, Cl., Wu, S. et al. Analysis of genetically engineered oncolytic herpes simplex viruses in human prostate cancer organotypic cultures. Gene Ther 16, 1477–1482 (2009). https://doi.org/10.1038/gt.2009.94

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