A Comparative Safety Profile Assessment of Oncolytic Virus Therapy Based on Clinical Trials

Abstract

Oncolytic virus therapy (OVT) represents a new class of therapeutic agents in cancer treatment. The molecular and cellular mechanisms of action of OVTs have been evaluated in nonclinical/clinical phase trials. Various genetically modified viruses have been developed as oncolytic agents, and the first approval of an OVT for clinical use was issued by the US Food and Drug Administration in 2015. In this context, more and more clinical development of OVTs is anticipated in the future. This article provides a risk assessment of OVT based on the safety data obtained from all clinical trials to date using a publicly available database. The most common adverse events (AEs) observed in clinical trials have been infection-related symptoms such as fatigue, chills, fever, and nausea; few serious AEs have been observed, regardless of the kind of virus or transfected genes. In vivo systemic infusion of OVTs demonstrated a high percentage of AEs, but most AEs were manageable using common drugs. This paper describes OVTs' specific safety/toxicity profiles and encourages the performance of further clinical trials of OVTs to address the most serious challenges anticipated in the development of OVTs as a new class of drugs for the treatment of cancer.

Biodistribution Analysis of Oncolytic Adenoviruses in Canine Patient Necropsy Samples Treated with Cellular Virotherapy

“…The most common side effects were fatigue, nausea/vomiting, chills, and pain, all well-known infection-related symptoms. 19 Our data with Celyvir are similar in human and canine patients, with excellent tolerance of the treatment in most cases, resulting in no clinical secondary effects. However, there is a lack of knowledge about the biodistribution of the viruses after administration in patients.…”

STAT3/5 Inhibitors Suppress Proliferation in Bladder Cancer and Enhance Oncolytic Adenovirus Therapy

“…A multitude of viruses from vesicular stomatitis virus, vaccinia virus or adenovirus are at various stages in clinical trials and most of them have a remarkable safety profile. Most side effects are infection-related or nausea and are easily manageable [36]. At preclinical level, it has been shown that oncolytic adenoviruses are successful in treating MIBC [37].…”

Neural Stem Cells Improve the Delivery of Oncolytic Chimeric Orthopoxvirus in a Metastatic Ovarian Cancer Model

“…For example, it was recently shown that a low dose of 10 4 PFUs of CF33 in a preclinical flank setting slowed pancreatic tumor progression without measurable toxicities associated with virotherapy. 25 , 37 …”

“…For example, it was recently shown that a low dose of 10 4 PFUs of CF33 in a preclinical flank setting slowed pancreatic tumor progression without measurable toxicities associated with virotherapy. 25,37 We have previously shown that the HB1.F3.CD cell line enhances adenoviral delivery to brain and peritoneal cancers; however, HB1.F3.CD-encapsulated pox virus delivery was not tested. In the current study, we utilized a research lot of HB1.F3.CD, equivalent to the clinical lot used in the glioma clinical trial (ClinicalTrials.gov: NCT03072134) to package CF33.…”