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Published on: April 27, 2018
Reovirus mutant jin-3 exhibits lytic and immune-stimulatory effects in preclinical human prostate cancer models
Arjanneke F van de Merbel1, Geertje van der Horst1, Maaike H van der Mark1
1Department of Urology, Leiden University Medical Center, Leiden, The Netherlands.
Abstract:
Treatment of castration-resistant prostate cancer remains a challenging clinical problem. Despite the promising effects of immunotherapy in other solid cancers, prostate cancer has remained largely unresponsive. Oncolytic viruses represent a promising therapeutic avenue, as oncolytic virus treatment combines tumour cell lysis with activation of the immune system and mounting of effective anti-tumour responses. Mammalian Orthoreoviruses are non-pathogenic human viruses with a preference of lytic replication in human tumour cells. In this study, we evaluated the oncolytic efficacy of the bioselected oncolytic reovirus mutant jin-3 in multiple human prostate cancer models. The jin-3 reovirus displayed efficient infection, replication, and anti-cancer responses in 2D and 3D prostate cancer models, as well as in ex vivo cultured human tumour slices. In addition, the jin-3 reovirus markedly reduced the viability and growth of human cancer cell lines and patient-derived xenografts. The infection induced the expression of mediators of immunogenic cell death, interferon-stimulated genes, and inflammatory cytokines. Taken together, our data demonstrate that the reovirus mutant jin-3 displays tumour tropism, and induces potent oncolytic and immunomodulatory responses in human prostate cancer models. Therefore, jin-3 reovirus represents an attractive candidate for further development as oncolytic agent for treatment of patients with aggressive localised or advanced prostate cancer.
Insights
The reovirus mutant jin-3 effectively targets and replicates in prostate cancer cells, offering a new oncolytic virus therapy. This promising treatment activates anti-cancer immune responses for aggressive prostate cancer.
Area of Science:
- Oncology
- Virology
- Immunotherapy
Background:
- Castration-resistant prostate cancer (CRPC) is difficult to treat.
- Prostate cancer is largely unresponsive to current immunotherapies.
- Oncolytic viruses offer a novel therapeutic strategy by directly killing tumor cells and stimulating anti-tumor immunity.
Purpose of the Study:
- To evaluate the oncolytic efficacy of the reovirus mutant jin-3 in human prostate cancer models.
- To assess the anti-cancer responses induced by jin-3 reovirus.
- To determine the potential of jin-3 reovirus as a therapeutic agent for prostate cancer.
Main Methods:
- Testing jin-3 reovirus in 2D and 3D prostate cancer cell cultures.
- Evaluating jin-3 reovirus in ex vivo human tumor slices and patient-derived xenografts.
- Analyzing the expression of immune mediators, interferon-stimulated genes, and cytokines post-infection.
Main Results:
- Jin-3 reovirus demonstrated efficient infection, replication, and anti-cancer activity in various prostate cancer models.
- The virus significantly reduced the viability and growth of human cancer cell lines and xenografts.
- Infection with jin-3 reovirus induced immunogenic cell death, interferon-stimulated genes, and inflammatory cytokines.
Conclusions:
- The reovirus mutant jin-3 exhibits tumor tropism and potent oncolytic and immunomodulatory effects in human prostate cancer.
- Jin-3 reovirus is a promising candidate for treating aggressive localized or advanced prostate cancer.
- Further development of jin-3 reovirus as an oncolytic agent is warranted.
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