Oncolytic viruses: From bench to bedside with a focus on safety

Abstract

Oncolytic viruses are a relatively new class of anti-cancer immunotherapy agents. Several viruses have undergone evaluation in clinical trials in the last decades, and the first agent is about to be approved to be used as a novel cancer therapy modality. In the current review, an overview is presented on recent (pre)clinical developments in the field of oncolytic viruses that have previously been or currently are being evaluated in clinical trials. Special attention is given to possible safety issues like toxicity, environmental shedding, mutation and reversion to wildtype virus.

Keywords: CAR, Coxsackie Adenovirus receptor; CD, cytosine deaminase; CEA, carcinoembryonic antigen; CVA, Coxsackievirus type A; DAF, decay accelerating factor; DNA, DNA; EEV, extracellular enveloped virus; EGF, epidermal growth factor; EGF-R, EGF receptor; EMA, European Medicines Agency; FDA, Food and Drug Administration; GBM, glioblastoma multiforme; GM-CSF, granulocyte-macrophage colony-stimulating factor; HA, hemagglutinin; HAdV, Human (mast)adenovirus; HER2, human epidermal growth factor receptor 2; HSV, herpes simplex virus; ICAM-1, intercellular adhesion molecule 1; IFN, interferon; IRES, internal ribosome entry site; KRAS, Kirsten rat sarcoma viral oncogene homolog; Kb, kilobase pairs; MeV, Measles virus; MuLV, Murine leukemia virus; NDV, Newcastle disease virus; NIS, sodium/iodide symporter; NSCLC, non-small cell lung carcinoma; OV, oncolytic virus; PEG, polyethylene glycol; PKR, protein kinase R; PV, Polio virus; RCR, replication competent retrovirus; RCT, randomized controlled trial; RGD, arginylglycylaspartic acid (Arg-Gly-Asp); RNA, ribonucleic acid; Rb, retinoblastoma; SVV, Seneca Valley virus; TGFα, transforming growth factor α; VGF, Vaccinia growth factor; VSV, Vesicular stomatitis virus; VV, Vaccinia virus; cancer; crHAdV, conditionally replicating HAdV; dsDNA, double stranded DNA; dsRNA, double stranded RNA; environment; hIFNβ, human IFN β; immunotherapy; mORV, Mammalian orthoreovirus; mORV-T3D, mORV type 3 Dearing; oHSV, oncolytic HSV; oncolytic virotherapy; oncolytic virus; rdHAdV, replication-deficient HAdV; review; safety; shedding; ssRNA, single stranded RNA; tk, thymidine kinase.