Reovirus mutant jin-3 exhibits lytic and immune-stimulatory effects in preclinical human prostate cancer models

Arjanneke F. van de Merbel, Geertje van der Horst, Maaike H. van der Mark, Selas T.F. Bots, Diana J.M. van den Wollenberg, Corrina M.A. de Ridder, Debra Stuurman, Tilly Aalders, Sigrun Erkens-Schulz, Nadine van Montfoort, Wouter R. Karthaus, Niven Mehra, Minke Smits, Jack A. Schalken, Wytske M. van Weerden, Rob C. Hoeben, Gabri van der Pluijm*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)793-802
Number of pages10
JournalCancer Gene Therapy
Volume29
Issue number6
DOIs
Publication statusPublished - 16 Jun 2021

Bibliographical note

Funding Information:
This study was supported by a personalised medicine grant from the Dutch Cancer Society (KWF) Alpe D’HuZes (UL2014-7058), OAK Foundation (SOAK 18.01 and SOAK-Strati-Vir project), and a kind gift from the Franje Foundation.

Publisher Copyright:
© 2021, The Author(s).

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