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Updated: Mar 15, 2026
Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
High-throughput screening to enhance oncolytic virus immunotherapy
K J Allan1, David F Stojdl2, S L Swift3
1Children's Hospital of Eastern Ontario (CHEO) Research Institute; Department of Biology, Microbiology and Immunology.
Abstract:
High-throughput screens can rapidly scan and capture large amounts of information across multiple biological parameters. Although many screens have been designed to uncover potential new therapeutic targets capable of crippling viruses that cause disease, there have been relatively few directed at improving the efficacy of viruses that are used to treat disease. Oncolytic viruses (OVs) are biotherapeutic agents with an inherent specificity for treating malignant disease. Certain OV platforms - including those based on herpes simplex virus, reovirus, and vaccinia virus - have shown success against solid tumors in advanced clinical trials. Yet, many of these OVs have only undergone minimal engineering to solidify tumor specificity, with few extra modifications to manipulate additional factors. Several aspects of the interaction between an OV and a tumor-bearing host have clear value as targets to improve therapeutic outcomes. At the virus level, these include delivery to the tumor, infectivity, productivity, oncolysis, bystander killing, spread, and persistence. At the host level, these include engaging the immune system and manipulating the tumor microenvironment. Here, we review the chemical- and genome-based high-throughput screens that have been performed to manipulate such parameters during OV infection and analyze their impact on therapeutic efficacy. We further explore emerging themes that represent key areas of focus for future research.
Insights
High-throughput screens are advancing oncolytic virus (OV) therapy by optimizing viral delivery, tumor targeting, and immune engagement for enhanced cancer treatment efficacy.
Area of Science:
- Oncology
- Virology
- Biotechnology
Background:
- Oncolytic viruses (OVs) are promising biotherapeutics for cancer treatment, with platforms like herpes simplex virus, reovirus, and vaccinia virus showing success in clinical trials.
- Current OV engineering primarily focuses on tumor specificity, with limited manipulation of other factors influencing therapeutic outcomes.
- Key parameters for improving OV efficacy include viral delivery, infectivity, productivity, oncolysis, bystander killing, spread, persistence, immune system engagement, and tumor microenvironment modulation.
Purpose of the Study:
- To review chemical- and genome-based high-throughput screens used to enhance OV therapeutic efficacy.
- To analyze the impact of these screens on OV-mediated cancer treatment.
- To identify emerging themes and future research directions in OV engineering.
Main Methods:
- Review of literature on high-throughput screening methodologies (chemical and genomic) applied to oncolytic viruses.
- Analysis of studies reporting modifications to OV parameters (viral and host levels) and their effects on therapeutic outcomes.
- Synthesis of findings to identify trends and future research opportunities.
Main Results:
- High-throughput screens offer powerful tools for optimizing OV properties such as tumor targeting, replication, and immune modulation.
- Engineering efforts have successfully improved viral delivery, oncolysis, and immune engagement, leading to enhanced therapeutic efficacy in preclinical and clinical settings.
- Significant advancements have been made in manipulating both viral and host factors to improve OV performance.
Conclusions:
- High-throughput screening is crucial for accelerating the development of more effective oncolytic virus therapies.
- Future research should focus on integrated approaches combining viral engineering with host-directed strategies to maximize therapeutic potential.
- Continued exploration of novel screening platforms and engineering targets will be vital for overcoming current limitations in OV therapy.
