Prior Exposure to Coxsackievirus A21 Does Not Mitigate Oncolytic Therapeutic Efficacy

Oncolytic viruses (OVs) are being developed as a type of immunotherapy and have demonstrated durable tumor responses and clinical efficacy. One such OV, Coxsackievirus A21 (CVA21), exhibited therapeutic efficacy in early phase clinical trials, demonstrating the ability to infect and kill cancer cell...

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Main Authors: William J. Burnett, David M. Burnett, Gennie Parkman, Andrew Ramstead, Nico Contreras, William Gravley, Sheri L. Holmen, Matthew A. Williams, Matthew W. VanBrocklin
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/17/4462
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spelling doaj-2549aa6765f34521bde163826e5fe16b2021-09-09T13:41:07ZengMDPI AGCancers2072-66942021-09-01134462446210.3390/cancers13174462Prior Exposure to Coxsackievirus A21 Does Not Mitigate Oncolytic Therapeutic EfficacyWilliam J. Burnett0David M. Burnett1Gennie Parkman2Andrew Ramstead3Nico Contreras4William Gravley5Sheri L. Holmen6Matthew A. Williams7Matthew W. VanBrocklin8Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADepartment of Pathology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADepartment of Pathology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USASchool of Medicine, University of Nevada Las Vegas, Las Vegas, NV 89154, USADepartment of Surgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADepartment of Pathology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADepartment of Surgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USAOncolytic viruses (OVs) are being developed as a type of immunotherapy and have demonstrated durable tumor responses and clinical efficacy. One such OV, Coxsackievirus A21 (CVA21), exhibited therapeutic efficacy in early phase clinical trials, demonstrating the ability to infect and kill cancer cells and stimulate anti-tumor immune responses. However, one of the major concerns in using this common cold virus as a therapeutic is the potential for innate and adaptive immune responses to mitigate the benefits of viral infection, particularly in individuals that have been exposed to coxsackievirus prior to treatment. In this study, we assess melanoma responses to CVA21 in the absence or presence of prior exposure to the virus. Melanomas were transplanted into naïve or CVA21-immunized C57BL6 mice and the mice were treated with intratumoral (IT) CVA21. We find that prior exposure to CVA21 does not dramatically affect tumor responses, nor does it alter overall survival. Our results suggest that prior exposure to coxsackievirus is not a critical determinant of patient selection for IT CVA21 interventions.https://www.mdpi.com/2072-6694/13/17/4462oncolytic viruscoxsackievirusCVA21virotherapypicornavirusimmunotherapy
collection DOAJ
language English
format Article
sources DOAJ
author William J. Burnett
David M. Burnett
Gennie Parkman
Andrew Ramstead
Nico Contreras
William Gravley
Sheri L. Holmen
Matthew A. Williams
Matthew W. VanBrocklin
spellingShingle William J. Burnett
David M. Burnett
Gennie Parkman
Andrew Ramstead
Nico Contreras
William Gravley
Sheri L. Holmen
Matthew A. Williams
Matthew W. VanBrocklin
Prior Exposure to Coxsackievirus A21 Does Not Mitigate Oncolytic Therapeutic Efficacy
Cancers
oncolytic virus
coxsackievirus
CVA21
virotherapy
picornavirus
immunotherapy
author_facet William J. Burnett
David M. Burnett
Gennie Parkman
Andrew Ramstead
Nico Contreras
William Gravley
Sheri L. Holmen
Matthew A. Williams
Matthew W. VanBrocklin
author_sort William J. Burnett
title Prior Exposure to Coxsackievirus A21 Does Not Mitigate Oncolytic Therapeutic Efficacy
title_short Prior Exposure to Coxsackievirus A21 Does Not Mitigate Oncolytic Therapeutic Efficacy
title_full Prior Exposure to Coxsackievirus A21 Does Not Mitigate Oncolytic Therapeutic Efficacy
title_fullStr Prior Exposure to Coxsackievirus A21 Does Not Mitigate Oncolytic Therapeutic Efficacy
title_full_unstemmed Prior Exposure to Coxsackievirus A21 Does Not Mitigate Oncolytic Therapeutic Efficacy
title_sort prior exposure to coxsackievirus a21 does not mitigate oncolytic therapeutic efficacy
publisher MDPI AG
series Cancers
issn 2072-6694
publishDate 2021-09-01
description Oncolytic viruses (OVs) are being developed as a type of immunotherapy and have demonstrated durable tumor responses and clinical efficacy. One such OV, Coxsackievirus A21 (CVA21), exhibited therapeutic efficacy in early phase clinical trials, demonstrating the ability to infect and kill cancer cells and stimulate anti-tumor immune responses. However, one of the major concerns in using this common cold virus as a therapeutic is the potential for innate and adaptive immune responses to mitigate the benefits of viral infection, particularly in individuals that have been exposed to coxsackievirus prior to treatment. In this study, we assess melanoma responses to CVA21 in the absence or presence of prior exposure to the virus. Melanomas were transplanted into naïve or CVA21-immunized C57BL6 mice and the mice were treated with intratumoral (IT) CVA21. We find that prior exposure to CVA21 does not dramatically affect tumor responses, nor does it alter overall survival. Our results suggest that prior exposure to coxsackievirus is not a critical determinant of patient selection for IT CVA21 interventions.
topic oncolytic virus
coxsackievirus
CVA21
virotherapy
picornavirus
immunotherapy
url https://www.mdpi.com/2072-6694/13/17/4462
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