Immunovirotherapy for the Treatment of Glioblastoma and Other Malignant Gliomas

Estévez-Ordoñez, Dagoberto; Chagoya, Gustavo; Salehani, Arsalaan; Atchley, Travis J.; Laskay, Nicholas M B; Parr, Matthew S.; Elsayed, Galal; Mahavadi, Anil; Rahm, Sage; Friedman, Gregory K.; Markert, James M.

doi:10.1016/j.nec.2020.12.008

Cited by 18 publications

(17 citation statements)

References 123 publications

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“…MV expressing carcinoembryonic antigen gene (MV-CEA) is an attenuated strain of MV used for human vaccination (Lin and Richardson, 2016). Subsequent analyses retargeted MVs to the epidermal growth factor receptor, EGF receptor variant III, and the IL-13Rα2 receptor to increase their specificity for GBM (Estevez-Ordonez et al, 2021; Figure 1C). The expression of the sodium iodide transporter MV (MV-NIS) not only tracks the viral infection efficiency but also potentially improves the therapeutic efficacy by allowing the intracellular uptake of I-131 (Aref et al, 2016).…”

Section: Oncolytic MVmentioning

confidence: 99%

Glioblastoma microenvironment and its reprogramming by oncolytic virotherapy

Long

Liu

et al. 2022

Front. Cell. Neurosci.

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Glioblastoma (GBM), a highly aggressive form of brain tumor, responds poorly to current conventional therapies, including surgery, radiation therapy, and systemic chemotherapy. The reason is that the delicate location of the primary tumor and the existence of the blood-brain barrier limit the effectiveness of traditional local and systemic therapies. The immunosuppressive status and multiple carcinogenic pathways in the complex GBM microenvironment also pose challenges for immunotherapy and single-targeted therapy. With an improving understanding of the GBM microenvironment, it has become possible to consider the immunosuppressive and highly angiogenic GBM microenvironment as an excellent opportunity to improve the existing therapeutic efficacy. Oncolytic virus therapy can exert antitumor effects on various components of the GBM microenvironment. In this review, we have focused on the current status of oncolytic virus therapy for GBM and the related literature on antitumor mechanisms. Moreover, the limitations of oncolytic virus therapy as a monotherapy and future directions that may enhance the field have also been discussed.

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Section: Oncolytic MVmentioning

confidence: 99%

Glioblastoma microenvironment and its reprogramming by oncolytic virotherapy

Long

Liu

et al. 2022

Front. Cell. Neurosci.

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“…32 Several types of oncolytic viruses have been developed as cancer therapeutics, including adenovirus, herpesvirus, measles virus, coxsackievirus, reovirus, retrovirus, and vesicular stomatitis virus. 33 One oncolytic virus that has been extensively evaluated using the WoO design is Delta-24-RGD (DNX2401), an oncolytic adenovirus. This agent has been evaluated in a phase I, dose-escalation, WoO clinical trial of intratumorally injected Delta-24-RGD in 37 patients with recurrent malignant glioma.…”

Section: Use Of Woo Trials To Evaluate Oncolytic Viral Therapiesmentioning

confidence: 99%

A Window of Opportunity to Overcome Therapeutic Failure in Neuro-Oncology

Vogelbaum

Heimberger

et al. 2022

American Society of Clinical Oncology Educational Book

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Glioblastoma is the most common primary malignant brain neoplasm and it remains one of the most difficult-to-treat human cancers despite decades of discovery and translational and clinical research. Many advances have been made in our understanding of the genetics and epigenetics of gliomas in general; yet, there remains an urgent need to develop novel agents that will improve the survival of patients with this deadly disease. What sets glioblastoma apart from all other cancers is that it develops and spreads within an organ that renders tumor cells inaccessible to most systemically administered agents because of the presence of the blood-brain barrier. Inadequate drug penetration into the central nervous system is often cited as the most common cause of trial failure in neuro-oncology, and even so-called brain-penetrant therapeutics may not reach biologically relevant concentrations in tumor cells. Evaluation of the pharmacokinetics and pharmacodynamics of a novel therapy is a cornerstone of drug development, but few trials for glioma therapeutics have incorporated these basic elements in an organ-specific manner. Window-of-opportunity clinical trial designs can provide early insight into the biological plausibility of a novel therapeutic strategy in the clinical setting. A variety of window-of-opportunity trial designs, which take into account the limited access to treated tissue and the challenges with obtaining pretreatment control tissues, have been used for the initial development of traditional and targeted small-molecule drugs and biologic therapies, including immunotherapies and oncolytic viral therapies. Early-stage development of glioma therapeutics should include a window-of-opportunity component whenever feasible.

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“…These present and behave much like gliomas in humans with similar radiographic, histopathologic, and genetic features. In the dog, high-grade oligodendrogliomas have been shown to be more similar to human glioblastoma multiforme than to human high-grade oligodendroglioma, typically lacking the favorable IDH mutation and 1p19q co-deletion [20] . They also respond to therapies much like their human counterparts [20] .…”

Section: Translational Modelmentioning

confidence: 99%

“…In the dog, high-grade oligodendrogliomas have been shown to be more similar to human glioblastoma multiforme than to human high-grade oligodendroglioma, typically lacking the favorable IDH mutation and 1p19q co-deletion [20] . They also respond to therapies much like their human counterparts [20] . Current standard of care for gliomas in both pet dogs and humans is a combination of maximum safe resection, chemotherapy, and radiation.…”

Section: Translational Modelmentioning

confidence: 99%

Evaluation of immunologic parameters in canine glioma patients treated with an oncolytic herpes virus

Chambers¹,

Foote²,

Bentley³

et al. 2021

jtgg

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Aim: To molecularly characterize the tumor microenvironment and evaluate immunologic parameters in canine glioma patients before and after treatment with oncolytic human IL-12-expressing herpes simplex virus (M032) and in treatment naïve canine gliomas. Methods: We assessed pet dogs with sporadically occurring gliomas enrolled in Stage 1 of a veterinary clinical trial that was designed to establish the safety of intratumoral oncoviral therapy with M032, a genetically modified oncolytic herpes simplex virus. Specimens from dogs in the trial and dogs not enrolled in the trial were evaluated with immunohistochemistry, NanoString, Luminex cytokine profiling, and multi-parameter flow cytometry. Results: Treatment-naive canine glioma microenvironment had enrichment of Iba1 positive macrophages and minimal numbers of T and B cells, consistent with previous studies identifying these tumors as immunologically “cold”. NanoString mRNA profiling revealed enrichment for tumor intrinsic pathways consistent with suppression of tumor-specific immunity and support of tumor progression. Oncolytic viral treatment induced an intratumoral mRNA transcription signature of tumor-specific immune responses in 83% (5/6) of canine glioma patients. Changes included mRNA signatures corresponding with interferon signaling, lymphoid and myeloid cell activation, recruitment, and T and B cell immunity. Multiplexed protein analysis identified a subset of oligodendroglioma subjects with increased concentrations of IL-2, IL-7, IL-6, IL-10, IL-15, TNFα, GM-CSF between 14 and 28 days after treatment, with evidence of CD4+ T cell activation and modulation of IL-4 and IFNγ production in CD4+ and CD8+ T cells isolated from peripheral blood. Conclusion: These findings indicate that M032 modulates the tumor-immune microenvironment in the canine glioma model.

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Immunovirotherapy for the Treatment of Glioblastoma and Other Malignant Gliomas

Cited by 18 publications

References 123 publications

Glioblastoma microenvironment and its reprogramming by oncolytic virotherapy

Glioblastoma microenvironment and its reprogramming by oncolytic virotherapy

A Window of Opportunity to Overcome Therapeutic Failure in Neuro-Oncology

Evaluation of immunologic parameters in canine glioma patients treated with an oncolytic herpes virus

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