Oncolytic viruses as experimental treatments for malignant gliomas: Using a scourge to treat a devil

Zemp, Franz J.; Corredor, Juan Carlos; Lun, Xueqing; Muruve, Daniel A.; Forsyth, Peter

doi:10.1016/j.cytogfr.2010.04.001

Cited by 56 publications

(70 citation statements)

References 181 publications

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“…Oncolytic virus refer to the virus that kills tumor cells selectively without harming the normal surrounding tissue (Biederer et al, 2002;Franz et al, 2010). As a mode of therapy, oncolytic virus is used to "self-recognize" and infect the mutated cancerous cells which replicates within the infected cells followed by release of new virion that simultaneously amplifies the input dose.…”

Section: Oncolytic Virus Therapymentioning

confidence: 99%

“…On the other hand, normal brain cells response to the viral infections leads to stimulation of the patern-recognition-receptors (PRRs) and later activates the Type 1 interferon. ( Franz et al, 2010). The type 1 interferon futher binds and activates the Janus kinases JAK1 and TYK2 which inturns phophorylates the activators for transcription of STAT1 and STAT2.…”

Section: Glioblastoma and Oncolytic Selective Mechanismmentioning

confidence: 99%

“…Rac1 is a key contributor to glioma cell survival, probably via multiple signaling pathways including JNK (Halatsch et al, 2009) but is found to be critical for the replication of oncolytic NDV to the highly tumorigenic ras-transformed skin carcinoma cells However, despite several entry-line association, there are several physicals barriers that is present in the gliomas microenvironment that blocks the virus distribution. The extracellular matrix (ECM), hypoxic region, and high interstitial pressure are amongst the major challenge in achieving lasting oncolytic virus infection (Franz et al, 2010) Besides that, GBM is currently described with multiple interactive dysregulated cell signalings pathway and this could lead to the inconsistency of outcome (Chamberline et al, 2006) in bigger population target.…”

Section: Glioblastoma and Oncolytic Selective Mechanismmentioning

confidence: 99%

“…Some anti-glioma activities were also found. Amongst these, NDV showed the most promising benefits with 6 patients showed tumor regression and 3 patients have long term survival (Franz et al, 2010). In this chapter, taking an example of Newcastle disease virus, we focus on the advantages of virotherapy, targeted pathway in oncolysis mechanism, methodology for virus with oncolytic properties study, and development of tumor model for glioma in a mouse model.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Targeted Therapy for Gliomas: the Oncolytic Virus Applications

Mustafa¹,

Roslan²,

Abdullah³

2011

Brain Tumors - Current and Emerging Therapeutic Strategies

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Section: Oncolytic Virus Therapymentioning

confidence: 99%

Section: Glioblastoma and Oncolytic Selective Mechanismmentioning

confidence: 99%

Section: Glioblastoma and Oncolytic Selective Mechanismmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Targeted Therapy for Gliomas: the Oncolytic Virus Applications

Mustafa¹,

Roslan²,

Abdullah³

2011

Brain Tumors - Current and Emerging Therapeutic Strategies

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“…42 In addition to their inherent cytotoxicity, oncolytic viruses can also be used as vectors for gene delivery. 40,41,43,44 contributing to the tumor microenvironment through promoting angiogenesis, stroma formation, and immunosuppressive effects. NSCs were the first stem/progenitor cells tested for homing to GBM tumors and are currently in clinical trial for GBM (Table II).…”

mentioning

confidence: 99%

Current Status of Gene Therapy for Brain Tumors∗

Ning

Rabkin

2015

Translating Gene Therapy to the Clinic

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Glioblastoma (GBM) is the most common and deadliest primary brain tumor in adults, with current treatments having limited impact on disease progression. Therefore the development of alternative treatment options is greatly needed. Gene therapy is a treatment strategy that relies on the delivery of genetic material, usually transgenes or viruses, into cells for therapeutic purposes, and has been applied to GBM with increasing promise. We have included selectively replicationcompetent oncolytic viruses within this strategy, although the virus acts directly as a complex biologic anti-tumor agent rather than as a classic gene delivery vehicle. GBM is a good candidate for gene therapy because tumors remain locally within the brain and only rarely metastasize to other tissues; the majority of cells in the brain are post-mitotic, which allows for specific targeting of dividing tumor cells; and tumors can often be accessed neurosurgically for administration of therapy. Delivery vehicles used for brain tumors include nonreplicating viral vectors, normal adult stem/progenitor cells, and oncolytic viruses. The therapeutic transgenes or viruses are typically cytotoxic or express prodrug activating suicide genes to kill glioma cells, immunostimulatory to induce or amplify anti-tumor immune responses, and/or modify the tumor microenvironment such as blocking angiogenesis. This review describes current preclinical and clinical gene therapy strategies for the treatment of glioma.Treating malignant gliomas, of which glioblastoma (GBM) is the most common and least curable, remains a daunting challenge even after substantial efforts to develop alternative therapies. The current standard of care is maximal surgical resection followed by radiation and temozolomide chemotherapy; however, the median survival still remains less than 15 months. 1,2 This poor survival is due to the aggressive and invasive nature of the tumor cells, resistance to treatment, and the challenges of delivering therapeutics into the brain. 3 GBM is thought to be derived from a small population of glioblastoma stem cells (GSCs), so-called because of their stem cell-like properties of self-renewal and multilineage differentiation while being highly tumorigenic. [4][5][6] GSCs have become an important model for studying GBM because their xenografts mimic the heterogeneous histopathology of the patient's tumor from which they were derived 7,8 and they remain genotypically similar to the patient's tumor, in contrast to serum-cultured cell lines. 9 These cells have provided insights into the origin of tumor-initiating cells and new targets for therapy. Other GBM animal models include established glioma cell lines (human and rodent) implanted intracranially into immunodeficient or immunocompetent animals, and genetically engineered mice that spontaneously develop brain tumors or are induced with viral vectors. 10 GENE DELIVERY VEHICLES FOR GLIOBLASTOMAMost gene therapies for GBM use biologic vectors such as viruses or cells. Replicationdefective or non-repli...

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Combination of fractionated irradiation with anti‐VEGF expressing vaccinia virus therapy enhances tumor control by simultaneous radiosensitization of tumor associated endothelium

Buckel

Advani

Frentzen

et al. 2013

Intl Journal of Cancer

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Oncolytic viruses are currently in clinical trials for a variety of tumors, including high grade gliomas. A characteristic feature of high grade gliomas is their high vascularity and treatment approaches targeting tumor endothelium are under investigation, including bevacizumab. The aim of this study was to improve oncolytic viral therapy by combining it with ionizing radiation and to radiosensitize tumor vasculature through a viral encoded anti-angiogenic payload. Here, we show how vaccinia virusmediated expression of a single-chain antibody targeting VEGF resulted in radiosensitization of the tumor-associated vasculature. Cell culture experiments demonstrated that purified vaccinia virus encoded antibody targeting VEGF reversed VEGFinduced radioresistance specifically in endothelial cells but not tumor cells. In a subcutaneous model of U-87 glioma, systemically administered oncolytic vaccinia virus expressing anti-VEGF antibody (GLV-1h164) in combination with fractionated irradiation resulted in enhanced tumor growth inhibition when compared to nonanti-VEGF expressing oncolytic virus (GLV-1h68) and irradiation. Irradiation of tumor xenografts resulted in an increase in VACV replication of both GLV-1h68 and GLV-1h164. However, GLV-1h164 in combination with irradiation resulted in a drastic decrease in intratumoral VEGF levels and tumor vessel numbers in comparison to GLV-1h68 and irradiation. These findings demonstrate the incorporation of an oncolytic virus expressing an anti-VEGF antibody (GLV-1h164) into a fractionated radiation scheme to target tumor cells by enhanced VACV replication in irradiated tumors as well as to radiosensitize tumor endothelium which results in enhanced efficacy of combination therapy of human glioma xenografts.Glioblastoma multiforme (GBM) is the most aggressive form of malignant primary brain tumors. The overall prognosis for patients diagnosed with GBM continues to remain poor with a median overall survival of 12-14 months with current therapies. Treatment for GBM includes maximal surgical resection followed by concurrent temozolomide and radiotherapy but the deeply infiltrating nature of GBM often precludes complete surgical excision. 1 A defining histologic feature of GBM is their high vascularity. To improve the therapeutic efficacy of radiotherapy for GBM, preclinical

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Oncolytic viruses as experimental treatments for malignant gliomas: Using a scourge to treat a devil

Cited by 56 publications

References 181 publications

Targeted Therapy for Gliomas: the Oncolytic Virus Applications

Targeted Therapy for Gliomas: the Oncolytic Virus Applications

Current Status of Gene Therapy for Brain Tumors∗

Combination of fractionated irradiation with anti‐VEGF expressing vaccinia virus therapy enhances tumor control by simultaneous radiosensitization of tumor associated endothelium

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