Personalizing Oncolytic Virotherapy for Glioblastoma: In Search of Biomarkers for Response

Stavrakaki, Eftychia; Dirven, Clemens; Lamfers, Martine L.M.

doi:10.3390/cancers13040614

Cited by 27 publications

(25 citation statements)

References 177 publications

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“…An ex vivo 3D tumor model generated from fresh tissue provides a culture condition that supports further researches into the dynamics of viral infection and the interaction with local immune system in the specific tumor microenvironment (304). With application of this system, it is possible to screen multiple OVs for a specific patient and establish the optimal OVT (224). Undoubtedly, identifying the optimal dosing, route of administration and schedule in OVs treatment requires further investigation.…”

Section: Future Directionsmentioning

confidence: 96%

“…Using OVs with knowledge of the specific mechanisms of their action will greatly benefit the OVT: appropriate markers can provide information about whether these mechanisms are working or not. More details on potential biomarkers for OVs in GBM were recently reviewed by Stavrakaki et al (224).…”

Section: Finding Suitable Markers For Evaluating the Effectiveness Of Therapymentioning

confidence: 99%

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Oncolytic Viro-Immunotherapy: An Emerging Option in the Treatment of Gliomas

Zeng

Sander³

et al. 2021

Front. Immunol.

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The prognosis of malignant gliomas remains poor, with median survival fewer than 20 months and a 5-year survival rate merely 5%. Their primary location in the central nervous system (CNS) and its immunosuppressive environment with little T cell infiltration has rendered cancer therapies mostly ineffective, and breakthrough therapies such as immune checkpoint inhibitors (ICIs) have shown limited benefit. However, tumor immunotherapy is developing rapidly and can help overcome these obstacles. But for now, malignant gliomas remain fatal with short survival and limited therapeutic options. Oncolytic virotherapy (OVT) is a unique antitumor immunotherapy wherein viruses selectively or preferentially kill tumor cells, replicate and spread through tumors while inducing antitumor immune responses. OVTs can also recondition the tumor microenvironment and improve the efficacy of other immunotherapies by escalating the infiltration of immune cells into tumors. Some OVTs can penetrate the blood-brain barrier (BBB) and possess tropism for the CNS, enabling intravenous delivery. Despite the therapeutic potential displayed by oncolytic viruses (OVs), optimizing OVT has proved challenging in clinical development, and marketing approvals for OVTs have been rare. In June 2021 however, as a genetically engineered OV based on herpes simplex virus-1 (G47Δ), teserpaturev got conditional and time-limited approval for the treatment of malignant gliomas in Japan. In this review, we summarize the current state of OVT, the synergistic effect of OVT in combination with other immunotherapies as well as the hurdles to successful clinical use. We also provide some suggestions to overcome the challenges in treating of gliomas.

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Section: Future Directionsmentioning

confidence: 96%

Section: Finding Suitable Markers For Evaluating the Effectiveness Of Therapymentioning

confidence: 99%

Oncolytic Viro-Immunotherapy: An Emerging Option in the Treatment of Gliomas

Zeng

Sander³

et al. 2021

Front. Immunol.

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“…Although oncolytic viruses can infect both normal and cancer cells, they can only replicate in cancer cells[ 217 ]. Preclinical and clinical trials have pointed to the capability of oncolytic viruses to stimulate antitumor immune responses by recruiting T cells (reviewed in[ 218 , 219 ]). It has been reported that the Zika virus exerts oncolytic activity against GSCs.…”

Section: Discussionmentioning

confidence: 99%

SOX transcription factors and glioma stem cells: Choosing between stemness and differentiation

Stevanović

Kovacevic-Grujicic

Mojsin

et al. 2021

WJSC

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Glioblastoma (GBM) is the most common, most aggressive and deadliest brain tumor. Recently, remarkable progress has been made towards understanding the cellular and molecular biology of gliomas. GBM tumor initiation, progression and relapse as well as resistance to treatments are associated with glioma stem cells (GSCs). GSCs exhibit a high proliferation rate and self-renewal capacity and the ability to differentiate into diverse cell types, generating a range of distinct cell types within the tumor, leading to cellular heterogeneity. GBM tumors may contain different subsets of GSCs, and some of them may adopt a quiescent state that protects them against chemotherapy and radiotherapy. GSCs enriched in recurrent gliomas acquire more aggressive and therapy-resistant properties, making them more malignant, able to rapidly spread. The impact of SOX transcription factors (TFs) on brain tumors has been extensively studied in the last decade. Almost all SOX genes are expressed in GBM, and their expression levels are associated with patient prognosis and survival. Numerous SOX TFs are involved in the maintenance of the stemness of GSCs or play a role in the initiation of GSC differentiation. The fine-tuning of SOX gene expression levels controls the balance between cell stemness and differentiation. Therefore, innovative therapies targeting SOX TFs are emerging as promising tools for combatting GBM. Combatting GBM has been a demanding and challenging goal for decades. The current therapeutic strategies have not yet provided a cure for GBM and have only resulted in a slight improvement in patient survival. Novel approaches will require the fine adjustment of multimodal therapeutic strategies that simultaneously target numerous hallmarks of cancer cells to win the battle against GBM.

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“…There is not, however, a generally accepted molecular biomarker used to predict response, though the following are associated with treatment response: tumor receptor expression, tumor mutation burden, and alterations to several molecular pathways including IFN expression, autophagy, and ubiquitination. 3,71,76,77 While only proposed, these data points may offer an insight into virus selection and response to treatment. Concerns remain about dosing protocols, genetic stability, viral integrity after replication, off-target replication, and immune-mediated clearance of OVs.…”

Section: Intratumoralmentioning

confidence: 99%

Oncolytic virus in gliomas: a review of human clinical investigations

Carpenter

Aiken

et al. 2021

Annals of Oncology

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Gliomas remain one of the more frustrating targets for oncologic therapy. Glioma resistance to conventional therapeutics is a product of their immune-privileged milieu behind the blood-brain barrier, in addition to their suppressive effect on the immune response itself. Taking the lead from the growing success of immunotherapy for systemic cancers, such as lung cancer and melanoma, immunotherapeutics has emerged as a major player in the potential treatment of gliomas, with oncolytic viruses in particular showing significant promise as evidenced by the recent Breakthrough and Fast Tract Designations for PVSRIPO and DNX2401. This review serves as a useful and updated compendium of the completed human clinical investigations for several oncolytic viruses in the treatment of gliomas.

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Personalizing Oncolytic Virotherapy for Glioblastoma: In Search of Biomarkers for Response

Cited by 27 publications

References 177 publications

Oncolytic Viro-Immunotherapy: An Emerging Option in the Treatment of Gliomas

Oncolytic Viro-Immunotherapy: An Emerging Option in the Treatment of Gliomas

SOX transcription factors and glioma stem cells: Choosing between stemness and differentiation

Oncolytic virus in gliomas: a review of human clinical investigations

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