Environmental safety evaluation of host range-modified oncolytic viruses: pivotal studies on reovirus and Newcastle disease virus

Samenvatting

Oncolytic viro-immunotherapy, based on oncolytic viruses (OVs), constitutes a novel treatment option for patients with aggressive cancers. Viro-immunotherapy results in direct tumour cell killing and local inflammation, which in turn leads to activation of the adaptive immune system. With the advent of reverse engineering techniques, modifications attributing to efficacy and safety of OVs have marked the introduction of new generations of recombinant OVs. We launched the Dutch Oncolytic Viro-ImmunoTherapy consortium (OVIT) to develop and implement viro-immunotherapeutic strategies with Newcastle disease virus (NDV) and mammalian reovirus (RV), for treatment of patients with currently untreatable aggressive cancers. Our project will generate OVs with improved oncolytic potency, which are being evaluated for efficacy in preclinical models.
Often, only limited information is available on the distribution, shedding, and survival in the environment for OVs. An environmental risk assessment (ERA) is necessary before clinical studies can start and assays for monitoring distribution and shedding of these OVs need to be developed. This study will provide data on host range-modified human viruses (RV), and attenuated avian viruses (NDV) to be used in oncolytic virotherapy. In addition, this study will provide data on human and animal viruses (RV and NDV respectively) to be used in oncolytic virotherapy for which host-range and/or virulence and/or immunogenic potential were increased on purpose. The generated data will allow an evidence-based ERA, which is necessary before clinical application of these viral agents can be initiated. In addition, these studies will serve as a paradigm for data acquisition on human and non-human genetically modified viruses with altered biological traits, that are rapidly gaining attention for use in oncolytic virotherapy globally.

Kenmerken

Projectnummer

15414

Hoofdaanvrager

Prof. dr. R.A.M. Fouchier

Verbonden aan

Erasmus Universiteit Rotterdam, Erasmus MC, Department of Viroscience

Uitvoerders

S. van Nieuwkoop, M.J.W.E. Rabelink

Looptijd

01/06/2017 tot 31/01/2022

Budget

€ 488.160