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Updated: Jun 20, 2026
Generation of Tumor Organoids from Genetically Engineered Mouse Models of Prostate Cancer
Published on: June 13, 2019
Analysis of genetically engineered oncolytic herpes simplex viruses in human prostate cancer organotypic cultures
B J Passer1, C-l Wu, S Wu
1Department of Neurosurgery, Brain Tumor Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. bpasser@partners.org
Abstract:
Oncolytic herpes simplex viruses type 1 (oHSVs) such as G47Delta 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 G47Delta 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 G47Delta generated approximately 30-fold more viral progeny than did G207. This correlated with the enhanced expression of G47Delta-derived glycoprotein gB protein levels as compared with G207. In benign prostate tissues, G207 and G47Delta 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.
Insights
Oncolytic herpes simplex viruses (oHSVs) like G47Delta and G207 show promise for prostate cancer treatment, selectively replicating in cancer cells. Human prostate organ cultures are valuable for studying oHSV tropism and specificity.
Area of Science:
- Oncolytic virotherapy
- Cancer biology
- Virology
Background:
- Genetically engineered oncolytic herpes simplex viruses type 1 (oHSVs), such as G47Delta and G207, are designed for selective replication in cancer cells.
- Factors influencing oHSV effectiveness include receptor expression, extracellular matrix, and cellular permissiveness.
Purpose of the Study:
- To investigate the tropism and replication of oHSVs in human prostate cancer using organ cultures.
- To compare the efficacy of G47Delta and G207 oHSVs in prostate cancer specimens.
Main Methods:
- Utilized human prostate organ cultures derived from radical prostatectomies.
- Infected organ cultures with G47Delta, G207, and wild-type HSV-1.
- Analyzed viral replication and progeny 3 days post-infection in cancer and benign prostate tissues.
Main Results:
- G47Delta and G207 selectively replicated in prostatic epithelial cancer cells, not stromal cells, unlike wild-type HSV-1.
- G47Delta produced approximately 30-fold more viral progeny than G207, correlating with higher glycoprotein gB expression.
- oHSV titers were reduced in benign prostate tissues compared to cancer tissues, while wild-type HSV-1 titers remained similar.
Conclusions:
- Oncolytic herpes vectors demonstrate target specificity and replication competence in human prostate cancer.
- Human prostate organ cultures are a useful model for assessing oHSV tropism and cellular specificity in prostate cancer.
