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Updated: Dec 26, 2025
Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
Virus-Receptor Interactions and Virus Neutralization: Insights for Oncolytic Virus Development
Nadishka Jayawardena1, John T Poirier2, Laura N Burga1
1Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Abstract:
Oncolytic viruses (OVs) are replication competent agents that selectively target cancer cells. After penetrating the tumor cell, viruses replicate and eventually trigger cell lysis, releasing the new viral progeny, which at their turn will attack and kill neighbouring cells. The ability of OVs to self-amplify within the tumor while sparing normal cells can provide several advantages including the capacity to encode and locally produce therapeutic protein payloads, and to prime the host immune system. OVs targeting of cancer cells is mediated by host factors that are differentially expressed between normal tissue and tumors, including viral receptors and internalization factors. In this review article, we will discuss the evolution of oncolytic viruses that have reached the stage of clinical trials, their mechanisms of oncolysis, cellular receptors, strategies for targeting cancers, viral neutralization and developments to bypass virus neutralization.
Insights
Oncolytic viruses (OVs) selectively destroy cancer cells by replicating within them and triggering lysis. These agents offer advantages like localized therapeutic protein production and immune system priming for cancer treatment.
Area of Science:
- Oncology
- Virology
- Immunotherapy
Background:
- Oncolytic viruses (OVs) are engineered or naturally occurring viruses that selectively infect and replicate in cancer cells, leading to tumor cell lysis.
- This replication process releases new viral progeny, which can then infect and destroy neighboring cancer cells, creating a self-amplifying therapeutic effect.
- OVs possess the unique ability to spare normal cells, making them a promising targeted cancer therapy.
Purpose of the Study:
- To review the advancements in oncolytic virus therapy, focusing on viruses that have progressed to clinical trials.
- To elucidate the mechanisms of oncolysis, including viral replication, cell lysis, and immune system modulation.
- To discuss strategies for enhancing OV targeting of cancer cells and overcoming challenges like viral neutralization.
Main Methods:
- Review of clinical trial data and scientific literature on oncolytic viruses.
- Analysis of the molecular mechanisms underlying OV replication and cancer cell targeting.
- Examination of host-virus interactions, including viral receptors and internalization factors.
- Discussion of strategies to improve OV efficacy and overcome immune responses.
Main Results:
- OVs demonstrate selective tumor cell targeting and lysis, with potential for self-amplification within tumors.
- The efficacy of OVs can be enhanced by engineering them to carry therapeutic payloads or to evade immune detection.
- Host factors, such as differentially expressed receptors, play a crucial role in OV tropism for cancer cells.
- Viral neutralization by the host immune system remains a significant challenge, necessitating strategies to bypass it.
Conclusions:
- Oncolytic viruses represent a promising and evolving therapeutic strategy for cancer treatment.
- Further research and clinical development are essential to optimize OV delivery, efficacy, and safety, particularly in overcoming viral neutralization.
- The ability of OVs to modulate the tumor microenvironment and prime the host immune system offers a powerful platform for combination therapies.
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