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Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
Potential for Improving Potency and Specificity of Reovirus Oncolysis with Next-Generation Reovirus Variants
Adil Mohamed1, Randal N Johnston2, Maya Shmulevitz3
1Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2E1, Canada. adilm@ualberta.ca.
Abstract:
Viruses that specifically replicate in tumor over normal cells offer promising cancer therapies. Oncolytic viruses (OV) not only kill the tumor cells directly; they also promote anti-tumor immunotherapeutic responses. Other major advantages of OVs are that they dose-escalate in tumors and can be genetically engineered to enhance potency and specificity. Unmodified wild type reovirus is a propitious OV currently in phase I-III clinical trials. This review summarizes modifications to reovirus that may improve potency and/or specificity during oncolysis. Classical genetics approaches have revealed reovirus variants with improved adaptation towards tumors or with enhanced ability to establish specific steps of virus replication and cell killing among transformed cells. The recent emergence of a reverse genetics system for reovirus has provided novel strategies to fine-tune reovirus proteins or introduce exogenous genes that could promote oncolytic activity. Over the next decade, these findings are likely to generate better-optimized second-generation reovirus vectors and improve the efficacy of oncolytic reotherapy.
Insights
Oncolytic viruses (OV) show promise for cancer therapy by targeting tumors. Modifications to reovirus, an OV, enhance its tumor-killing ability and specificity for improved cancer treatment.
Area of Science:
- Oncology
- Virology
- Immunotherapy
Background:
- Oncolytic viruses (OV) are a promising cancer therapy, selectively replicating in tumor cells while sparing normal cells.
- OVs offer direct tumor cell killing and stimulate anti-tumor immune responses.
- Advantages include tumor-specific dose escalation and potential for genetic engineering to enhance efficacy.
Purpose of the Study:
- To review modifications of reovirus, a wild-type OV in clinical trials, to improve its potency and specificity for cancer therapy.
- To explore how genetic and classical approaches can enhance reovirus-based oncolysis.
Main Methods:
- Review of classical genetics findings identifying reovirus variants with enhanced tumor adaptation and replication.
- Analysis of strategies utilizing the reovirus reverse genetics system to modify viral proteins and introduce exogenous genes.
Main Results:
- Classical genetics has yielded reovirus variants with improved tumor cell targeting and replication.
- Reverse genetics enables fine-tuning of reovirus proteins and gene expression for enhanced oncolytic activity.
Conclusions:
- Modifications to reovirus show potential for creating optimized second-generation oncolytic reovirus vectors.
- These advancements are expected to improve the efficacy of reovirus-based oncolytic immunotherapy in the next decade.
