Chikungunya-vesicular stomatitis chimeric virus targets and eliminates brain tumors

Zhang, Xue; Mao, Guochao; Pol, Anthony N. van den

doi:10.1016/j.virol.2018.06.018

Cited by 20 publications

(12 citation statements)

References 69 publications

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“…Another solution may be to administer virotherapy through implantable CED catheters, which can be left in place post-resection until surgery-associated inflammation has subsided, then used to infuse virotherapy into the resection cavity. Furthermore, some intravenously delivered virotherapies have shown potent migratory features in the preclinical setting, highlighting their utility for delivery that is both spatially and temporally separated from tumor resection 68,79 . Under the above proposed schedules, pre-treatment tissue samples would still be available for pharmacodynamic analysis.…”

Section: Discussionmentioning

confidence: 99%

Virus-Based Therapies for the Treatment of Recurrent High-Grade Glioma

Immidisetti¹,

Nwagwu²,

Adamson³

et al. 2020

Preprint

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As new treatment modalities are being explored in neuro-oncology, viruses are emerging as a promising class of therapeutics. Virotherapy consists of introduction of either wild-type or engineered viruses to the site of disease, where they exert anti-tumor effect. These viruses can either be non-lytic, in which case they are used to deliver gene therapy, or lytic, which induce tumor cell lysis and subsequent host immunologic response. Replication-competent viruses can then go on to further infect and lyse neighboring glioma cells. This treatment paradigm is being explored extensively in both preclinical and clinical studies for a variety of indications. Virus-based therapies are advantageous due to the natural susceptibility of glioma cells to viral infection, which improves therapeutic selectivity. Furthermore, lytic viruses expose glioma antigens to the host immune system and subsequently stimulate an immune response that specifically targets tumor cells. This review surveys the current landscape of oncolytic virotherapy clinical trials in high-grade glioma, summarizes preclinical experiences, identifies challenges associated with this modality across multiple trials, and highlights potential to integrate this therapeutic strategy into promising combinatory approaches.

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Section: Discussionmentioning

confidence: 99%

Virus-Based Therapies for the Treatment of Recurrent High-Grade Glioma

Immidisetti¹,

Nwagwu²,

Adamson³

et al. 2020

Preprint

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show abstract

“…In another study, neuron-targeting micro-RNA sequences (miRT124) introduced into the SFV4 strain generated increased oncolytic potency in human glioblastoma cell lines and resulted in virus replication in tumors, significant inhibition of tumor growth and prolonged survival after intraperitoneal administration in C57BL/6 mice implanted with CT-2A orthotopic gliomas [ 82 ]. A chimeric vector was engineered, where the VSV G protein was replaced by the CHIKV envelope proteins (E3-E2-6K-E1) [ 83 ]. The VSVΔG-CHIKV vector selectively infected and eliminated tumors and the survival of tumor-bearing mice was extended from 40 to 100 days.…”

Section: Vaccines Against Cancermentioning

confidence: 99%

Self-Amplifying RNA Viruses as RNA Vaccines

Lundström¹

2020

IJMS

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Single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses and rhabdoviruses are characterized by their capacity of highly efficient self-amplification of RNA in host cells, which make them attractive vehicles for vaccine development. Particularly, alphaviruses and flaviviruses can be administered as recombinant particles, layered DNA/RNA plasmid vectors carrying the RNA replicon and even RNA replicon molecules. Self-amplifying RNA viral vectors have been used for high level expression of viral and tumor antigens, which in immunization studies have elicited strong cellular and humoral immune responses in animal models. Vaccination has provided protection against challenges with lethal doses of viral pathogens and tumor cells. Moreover, clinical trials have demonstrated safe application of RNA viral vectors and even promising results in rhabdovirus-based phase III trials on an Ebola virus vaccine. Preclinical and clinical applications of self-amplifying RNA viral vectors have proven efficient for vaccine development and due to the presence of RNA replicons, amplification of RNA in host cells will generate superior immune responses with significantly reduced amounts of RNA delivered. The need for novel and efficient vaccines has become even more evident due to the global COVID-19 pandemic, which has further highlighted the urgency in challenging emerging diseases.

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“…Immunization with SIN-gp100-IL-18 DNA resulted in therapeutic effects, enhanced protection of malignant brain tumors, and significantly prolonged survival rates. A chimeric VSV vector where the VSV G protein was replaced by the CHIKV E3-E2-6K-E1 polyprotein (VSVΔG-CHIKV) showed selective infection and elimination of brain tumor cells [103]. Moreover, tumor-bearing mice showed extended survival for more than 100 days.…”

Section: Cancermentioning

confidence: 99%

Self-Replicating RNA Viruses for Vaccine Development Against Infectious Diseases and Cancer

Lundström¹

2021

Preprint

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Alphaviruses, flaviviruses, measles viruses and rhabdoviruses are enveloped single-stranded RNA viruses, which have been engineered as expression vector systems for recombinant protein expression and vaccine development. Due to the presence of non-structural genes encoding the replicase complex, a 200,000-fold amplification of viral RNA occurs in the cytoplasm of infected cells providing extreme transgene expression levels, which is why they are named self-replicating RNA viruses. Expression of surface proteins of pathogens causing infectious disease and tumor antigens provide the basis for vaccine development against infectious diseases and cancer. The self-replicating RNA viral vectors can be administered as replicon RNA, recombinant viral particles, or layered DNA/RNA replicons. Self-replicating RNA viral vectors have been applied for vaccine development against influenza virus, HIV, hepatitis B virus, human papilloma virus, Ebola virus and recently coronaviruses, especially SARS-CoV-2 the causative agent of the COVID-19 pandemic. Measles virus and rhabdovirus vector-based SARS-CoV-2 vaccine candidates have been subjected to clinical trials. Moreover, RNA vaccine candidates based on self-amplifying alphaviruses have also been evaluated in clinical settings. Various cancers such as brain, breast, lung, ovarian, prostate cancer and melanoma have also been targeted for vaccine development. Robust immune responses and protection have been demonstrated in animal models. Clinical trials have shown good safety and target-specific immune responses. Ervebo, the VSV-based vaccine against Ebola virus disease has been approved for human use.

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Chikungunya-vesicular stomatitis chimeric virus targets and eliminates brain tumors

Cited by 20 publications

References 69 publications

Virus-Based Therapies for the Treatment of Recurrent High-Grade Glioma

Virus-Based Therapies for the Treatment of Recurrent High-Grade Glioma

Self-Amplifying RNA Viruses as RNA Vaccines

Self-Replicating RNA Viruses for Vaccine Development Against Infectious Diseases and Cancer

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