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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Tumor Restrictions to Oncolytic Virus
Markus Vähä-Koskela1, Ari Hinkkanen2
1Institute of Biotechnology, University of Helsinki, Helsinki 00790, Finland. markus.vaha-koskela@helsinki.fi.
Abstract:
Oncolytic virotherapy has advanced since the days of its conception but therapeutic efficacy in the clinics does not seem to reach the same level as in animal models. One reason is premature oncolytic virus clearance in humans, which is a reasonable assumption considering the immune-stimulating nature of the oncolytic agents. However, several studies are beginning to reveal layers of restriction to oncolytic virotherapy that are present before an adaptive neutralizing immune response. Some of these barriers are present constitutively halting infection before it even begins, whereas others are raised by minute cues triggered by virus infection. Indeed, we and others have noticed that delivering viruses to tumors may not be the biggest obstacle to successful therapy, but instead the physical make-up of the tumor and its capacity to mount antiviral defenses seem to be the most important efficacy determinants. In this review, we summarize the constitutive and innate barriers to oncolytic virotherapy and discuss strategies to overcome them.
Insights
Oncolytic virotherapy faces challenges due to premature virus clearance and tumor defenses. This review explores innate barriers and strategies to improve oncolytic virus efficacy in cancer treatment.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Oncolytic virotherapy shows promise but clinical efficacy lags behind animal models.
- Premature clearance of oncolytic viruses by the immune system is a suspected cause.
- Emerging evidence suggests pre-existing and induced barriers limit therapy before adaptive immunity develops.
Purpose of the Study:
- To review constitutive and innate barriers to oncolytic virotherapy.
- To discuss strategies for overcoming these limitations.
Main Methods:
- Literature review of studies on oncolytic virotherapy.
- Analysis of factors affecting oncolytic virus efficacy in preclinical and clinical settings.
Main Results:
- Tumor physical characteristics and intrinsic antiviral defenses are critical efficacy determinants.
- Constitutive barriers block infection initiation, while innate responses are triggered by viral presence.
- These barriers precede adaptive immune responses.
Conclusions:
- Overcoming constitutive and innate barriers is crucial for enhancing oncolytic virotherapy success.
- Targeting tumor microenvironment and innate immunity can improve treatment outcomes.
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