MicroRNAs and oncolytic viruses

Ruiz, Autumn; Russell, Stephen J.

doi:10.1016/j.coviro.2015.03.007

Cited by 59 publications

(58 citation statements)

References 78 publications

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“…Therefore, measures were taken to protect normal liver cells. MicroRNA target sequences are useful tools for genetic engineering to obtain restricted oncolytic virus activity [20] . We included microRNA target sequences for the hepatocytespecific miR122 in the 3 ′ UTR of the E1A gene of the virus genome.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of AdVince, an Oncolytic Adenovirus Adapted for Treatment of Liver Metastases from Neuroendocrine Cancer

Leja-Jarblad²,

Loskog³

et al. 2016

Neuroendocrinology

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Cancer immunotherapy is becoming a cornerstone in the clinical care of cancer patients due to the breakthrough trials with immune checkpoint blockade antibodies and chimeric antigen receptor T cells. The next breakthrough in cancer immunotherapy is likely to be oncolytic viruses engineered to selectively kill tumor cells and deceive the immune system to believe that the tumor is a foreign entity that needs to be eradicated. We have developed AdVince, an oncolytic adenovirus for treatment of liver metastases from neuroendocrine tumor (NET). AdVince includes the gene promoter from human chromogranin A for selective replication in neuroendocrine cells, miR122 target sequences for reduced liver toxicity, and a cell-penetrating peptide in the capsid for increased infectivity of tumor cells and optimized spread within tumors. This paper describes the preclinical evaluation of AdVince on freshly isolated human gastrointestinal NET cells resected from liver metastases and freshly isolated human hepatocytes as well as in fresh human blood. AdVince selectively replicates in and kills NET cells. Approximately 73-fold higher concentration of AdVince is needed to induce a similar level of cytotoxicity in NET cells as in hepatocytes. AdVince did not activate complement or induce considerable amount of proinflammatory cytokines or chemokines in human blood. The data presented herein indicate that AdVince can be safely evaluated in a phase I/IIa clinical trial for patients with liver-dominant NET.

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Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of AdVince, an Oncolytic Adenovirus Adapted for Treatment of Liver Metastases from Neuroendocrine Cancer

Leja-Jarblad²,

Loskog³

et al. 2016

Neuroendocrinology

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“…This enables them to guide post-transcriptional silencing of their target genes and determine the differential expression between cancerous and normal tissues (24). The negative regulation in gene expression makes it possible to utilize these miRNAs to inhibit viral replication in normal cells (25,26). Aberrant expression of miRNAs has previously been observed in numerous types of cancer (27).…”

Section: Specificity Of Ov In Succumbing Tumor Cellsmentioning

confidence: 99%

Advances in the mechanisms of action of cancer-targeting oncolytic viruses (Review)

et al. 2018

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Abstract. Cancer virotherapy mediated by oncolytic viruses (OV), has emerged as a novel and effective strategy in cancer therapeutics. Preclinical models have demonstrated anticancer activity against numerous types of cancer. Currently, a number of recombinant viruses are in late phase clinical trials, many of which have demonstrated promising results regarding the safety and reliability of the treatments, particularly when combined with standard antineoplastic therapies. In addition to molecular-targeted therapeutics, genetic engineering of the viruses allows functional complementation to chemotherapy or radiotherapy agents. Co-administration of chemotherapy or radiotherapy is imperative for an effective treatment regime. Additionally, these approaches may be used in combination with current treatments to assist in cancer management. The near future may reveal whether this renewed interest in oncological virotherapy will result in meaningful therapeutic effects in patients. The aim of the present review was to highlight how the knowledge of oncolytic viral specificity and cytotoxicity has advanced in recent years, with a view to discuss OV in clinical application and the future directions of this field.

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“…Introduction of target sites for miRNAs downregulated explicitly in malignant cells can prevent viral replication in normal tissue [62][63][64]. Exchanging furin cleavage sites necessary for cleavage and activation of viral proteins with target sequences for tumor-specific matrix metalloproteinases represents another strategy to prevent off-tumor toxicity [63,65].…”

Section: Viral Life Cyclementioning

confidence: 99%

Fighting Cancer with Mathematics and Viruses

Santiago¹,

Heidbuechel²,

Kandell³

et al. 2017

Preprint

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After decades of research, oncolytic virotherapy has recently advanced to clinical application, and currently a multitude of novel agents and combination treatments are being evaluated for cancer therapy. Oncolytic agents preferentially replicate in tumor cells, inducing tumor cell lysis and complex anti-tumor effects, such as innate and adaptive immune responses and the destruction of tumor vasculature. With the availability of different vector platforms and the potential of both genetic engineering and combination regimens to enhance particular aspects of safety and efficacy, the identification of optimal treatments for patient subpopulations or even individual patients becomes a top priority. Mathematical modeling can provide support in this arena by making use of experimental and clinical data to generate hypotheses about the mechanisms underlying complex biology and, ultimately, predict optimal treatment protocols. Increasingly complex models can be applied to account for therapeutically relevant parameters such as components of the immune system. In this review, we describe current developments in oncolytic virotherapy and mathematical modeling to discuss the benefit of integrating different modeling approaches into biological and clinical experimentation. Conclusively, we propose a mutual combination of these fields of research for more efficient development and effective treatments.

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MicroRNAs and oncolytic viruses

Cited by 59 publications

References 78 publications

Preclinical Evaluation of AdVince, an Oncolytic Adenovirus Adapted for Treatment of Liver Metastases from Neuroendocrine Cancer

Preclinical Evaluation of AdVince, an Oncolytic Adenovirus Adapted for Treatment of Liver Metastases from Neuroendocrine Cancer

Advances in the mechanisms of action of cancer-targeting oncolytic viruses (Review)

Fighting Cancer with Mathematics and Viruses

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