Reovirus as an Oncolytic Agent Against Experimental Human Malignant Gliomas

Wilcox, M. Elizabeth; Yang, Wen Qing; Senger, Donna L.; Rewcastle, N. B.; Morris, Donald G.; Brasher, Penny; Zhong, Shuming; Johnston, Randal N.; Nishikawa, Sandi; Lee, P. W. K.; Forsyth, Peter

doi:10.1093/jnci/93.12.903

Cited by 204 publications

(148 citation statements)

References 30 publications

Supporting

Mentioning

137

Contrasting

Unclassified

Order By: Relevance

“…However, in RAS-negative fibroblasts, all reovirus subtypes did not show oncolytic activity. These observations are in accordance with previous studies (5,10,11,(14)(15)(16).…”

Section: Discussionsupporting

confidence: 94%

All reovirus subtypes show oncolytic potential in primary cells of human high-grade glioma

Alloussi

Alkassar²,

Urbschat³

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

Abstract. Reoviridae are non-human pathogenic viruses. The family of reoviridae consists of 4 different subtypes. Many studies have proven that the Dearing subtype 3 has oncolytic potential. This potential is related to the RAS protein expression in tumour cells. The aim of this study, was to investigate whether all reovirus subtypes have oncolytic potential and whether there are differences in their efficacy, in particular for high-grade glioma. To evaluate the oncolytic potential, we performed an in vitro head-to-head study for all reovirus subtypes in 5 primary cell cultures of high-grade gliomas. The oncolytic activity was determined using end-point titration with observation of the cytopathogenic effect. For measurement of RAS activity, we performed an immunofluorescent detection stain on all cell cultures. For quantification of the virus, an RT-PCR measurement for all subtypes was performed. All reovirus subtypes showed oncolytic activity in the observed glioma biopsies. These observations correlated with RAS overexpression in the observed cells. All glioma biopsies overexpressed the RAS protein. The quantitative oncolytic potential differed in relation to the single observed cell culture and in relation to the chosen reovirus subtype. To our knowledge, this is the first study showing oncolytic activity for all reovirus subtypes. We show the relationship and correlation between RAS protein overexpression and vulnerability of cells to reovirus. Efficacy of the different subtypes is interindividually different and cannot be forecast.

show abstract

“…However, in RAS-negative fibroblasts, all reovirus subtypes did not show oncolytic activity. These observations are in accordance with previous studies (5,10,11,(14)(15)(16).…”

Section: Discussionsupporting

confidence: 94%

All reovirus subtypes show oncolytic potential in primary cells of human high-grade glioma

Alloussi

Alkassar²,

Urbschat³

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…Reovirus efficiently destroys local as well as distant metastatic tumors in immunocompromised animals even after a single injection administered through intravenous, intraperitoneal, or intratumoral routes (25)(26)(27)(28). Tumor regression achieved during reovirus anticancer therapy is thought to be primarily mediated by direct destruction of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Reovirus Virotherapy Overrides Tumor Antigen Presentation Evasion and Promotes Protective Antitumor Immunity

Gujar

Marcato

Pan

et al. 2010

Molecular Cancer Therapeutics

105

View full text Add to dashboard Cite

Tumor-associated immunosuppressive strategies, such as lack of tumor antigen recognition and failure of lymphocyte activation and homing, resist the development of tumor-specific immunity and hamper the immune response-mediated elimination of cancerous cells. In this report, we show that reovirus virotherapy overrides such a tumor immune evasion and establishes clinically meaningful antitumor immunity capable of protecting against subsequent tumor challenge. Reovirus-mediated destruction of tumor cells facilitates the recognition of tumor antigens by promoting the display of otherwise inaccessible tumorspecific immunogenic peptides on the surface of dendritic cells (DC). Furthermore, on exposure to reovirus, DCs produce IL-1α, IL-1β, IL-6, IL-12p40/70, IL-17, CD30L, eotaxin, GM-CSF, KC, MCP-1, MCP-5, M-CSF, MIG, MIP-1α, RANTES, TNF-α, VCAM-1, VSGF, CXCL-16, AXL, and MCP-2; undergo maturation; and migrate into the tumor microenvironment along with CD8 T cells. These reovirus-activated DCs also acquire the capacity to prime tumor antigen-specific transgenic T cells in vitro and intrinsic antitumor T-cell response in vivo. Further, reovirus virotherapy augments the efficacy of DC-or T cell-based anticancer immunotherapies and synergistically enhances the survival in tumor-bearing mice. Most importantly, antitumor cellular immune responses initiated during reovirus oncotherapy protect the host against subsequent tumor challenge in a reovirus-independent but antigen-dependent manner. These reovirus oncotherapy-initiated antitumor immune responses represent an anticancer therapeutic entity that can maintain a long-term cancer-free health even after discontinuation of therapy.

show abstract

“…The virus is not linked to any known human diseases and is therefore considered to be benign. More recently however, reovirus has been shown to be an effective oncolytic agent against a variety of cancers (Wilcox et al, 2001;Hirasawa et al, 2002;Norman et al, 2002;Etoh et al, 2003;Kilani et al, 2003) including lymphomas . These studies led to clinical trials of reovirus as a cancer therapeutic (Morris et al, 2002).…”

mentioning

confidence: 99%

The oncolytic effect in vivo of reovirus on tumour cells that have survived reovirus cell killing in vitro

et al. 2006

View full text Add to dashboard Cite

The use of oncolytic viruses has received considerable attention in recent years and many viruses have proved to be effective against a variety of cancer models and a few are currently being used in clinical trials. However, the possible emergence and outcome of virus-resistant tumour cells has not been addressed. We previously reported the effective use of reovirus against lymphoid malignancies, including the Burkitt's lymphoma cell line Raji. Here we isolated in vitro persistently infected (PI) Raji cells, and cells 'cured' of persistent reovirus infection ('cured' cells). Both PI and cured Raji cells resisted reovirus infection and cell killing in vitro. In vivo, the PI cells were non-tumorigenic in SCID mice, but cured cells regained the parental cells' ability to form tumours. Tumour xenografts from the cured cells, however, were highly susceptible to reovirus oncolysis in vivo. This susceptibility was due to the proteolytic environment within tumours that facilitates reovirus infection and cell killing. Our results show that persistent infection by reovirus impedes tumour development and that although PI cells cleared of reovirus are tumorigenic, they are killed upon rechallenge with reovirus. Both the PI and cured states are therefore not likely to be significant barriers to reovirus oncolytic therapy.

show abstract

Reovirus as an Oncolytic Agent Against Experimental Human Malignant Gliomas

Abstract: Reovirus has potent activity against human malignant gliomas in vitro, in vivo, and ex vivo. Oncolysis with reovirus may be a potentially useful treatment for a broad range of human cancers.

Cited by 204 publications

References 30 publications

All reovirus subtypes show oncolytic potential in primary cells of human high-grade glioma

All reovirus subtypes show oncolytic potential in primary cells of human high-grade glioma

Reovirus Virotherapy Overrides Tumor Antigen Presentation Evasion and Promotes Protective Antitumor Immunity

The oncolytic effect in vivo of reovirus on tumour cells that have survived reovirus cell killing in vitro

Contact Info

Product

Resources

About