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Intravenous Oncolytic Vaccinia Virus Therapy Results in a Differential Immune Response between Cancer Patients
SIMPLE SUMMARY: Oncolytic viruses (OVs) have been extensively studied as an immunotherapeutic agent against a variety of cancers with some successes. Immunotherapeutic strategies, such as OVs, aim to transform an immunologically ‘cold’ tumour microenvironment into a more favourable inflammatory ‘hot...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103071/ https://www.ncbi.nlm.nih.gov/pubmed/35565310 http://dx.doi.org/10.3390/cancers14092181 |
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author | West, Emma J. Scott, Karen J. Tidswell, Emma Bendjama, Kaidre Stojkowitz, Nicolas Lusky, Monika Kurzawa, Marta Prasad, Raj Toogood, Giles Ralph, Christy Anthoney, D. Alan Melcher, Alan A. Collinson, Fiona J. Samson, Adel |
author_facet | West, Emma J. Scott, Karen J. Tidswell, Emma Bendjama, Kaidre Stojkowitz, Nicolas Lusky, Monika Kurzawa, Marta Prasad, Raj Toogood, Giles Ralph, Christy Anthoney, D. Alan Melcher, Alan A. Collinson, Fiona J. Samson, Adel |
author_sort | West, Emma J. |
collection | PubMed |
description | SIMPLE SUMMARY: Oncolytic viruses (OVs) have been extensively studied as an immunotherapeutic agent against a variety of cancers with some successes. Immunotherapeutic strategies, such as OVs, aim to transform an immunologically ‘cold’ tumour microenvironment into a more favourable inflammatory ‘hot’ tumour. However, it is evident that not all patients have a favourable response to treatment. Furthermore, reliable biomarkers able to predict a patient’s response to therapy have not yet been elucidated. We show evidence of a distinct immunologically exhausted profile in patients who do not respond to OV, which may pave the way for the development of predictive biomarkers leading to a more personalised approach to cancer treatment using combination therapies. ABSTRACT: Pexa-Vec is an engineered Wyeth-strain vaccinia oncolytic virus (OV), which has been tested extensively in clinical trials, demonstrating enhanced cytotoxic T cell infiltration into tumours following treatment. Favourable immune consequences to Pexa-Vec include the induction of an interferon (IFN) response, followed by inflammatory cytokine/chemokine secretion. This promotes tumour immune infiltration, innate and adaptive immune cell activation and T cell priming, culminating in targeted tumour cell killing, i.e., an immunologically ‘cold’ tumour microenvironment is transformed into a ‘hot’ tumour. However, as with all immunotherapies, not all patients respond in a uniformly favourable manner. Our study herein, shows a differential immune response by patients to intravenous Pexa-Vec therapy, whereby some patients responded to the virus in a typical and expected manner, demonstrating a significant IFN induction and subsequent peripheral immune activation. However, other patients experienced a markedly subdued immune response and appeared to exhibit an exhausted phenotype at baseline, characterised by higher baseline immune checkpoint expression and regulatory T cell (Treg) levels. This differential baseline immunological profile accurately predicted the subsequent response to Pexa-Vec and may, therefore, enable the development of predictive biomarkers for Pexa-Vec and OV therapies more widely. If confirmed in larger clinical trials, these immunological biomarkers may enable a personalised approach, whereby patients with an exhausted baseline immune profile are treated with immune checkpoint blockade, with the aim of reversing immune exhaustion, prior to or alongside OV therapy. |
format | Online Article Text |
id | pubmed-9103071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91030712022-05-14 Intravenous Oncolytic Vaccinia Virus Therapy Results in a Differential Immune Response between Cancer Patients West, Emma J. Scott, Karen J. Tidswell, Emma Bendjama, Kaidre Stojkowitz, Nicolas Lusky, Monika Kurzawa, Marta Prasad, Raj Toogood, Giles Ralph, Christy Anthoney, D. Alan Melcher, Alan A. Collinson, Fiona J. Samson, Adel Cancers (Basel) Article SIMPLE SUMMARY: Oncolytic viruses (OVs) have been extensively studied as an immunotherapeutic agent against a variety of cancers with some successes. Immunotherapeutic strategies, such as OVs, aim to transform an immunologically ‘cold’ tumour microenvironment into a more favourable inflammatory ‘hot’ tumour. However, it is evident that not all patients have a favourable response to treatment. Furthermore, reliable biomarkers able to predict a patient’s response to therapy have not yet been elucidated. We show evidence of a distinct immunologically exhausted profile in patients who do not respond to OV, which may pave the way for the development of predictive biomarkers leading to a more personalised approach to cancer treatment using combination therapies. ABSTRACT: Pexa-Vec is an engineered Wyeth-strain vaccinia oncolytic virus (OV), which has been tested extensively in clinical trials, demonstrating enhanced cytotoxic T cell infiltration into tumours following treatment. Favourable immune consequences to Pexa-Vec include the induction of an interferon (IFN) response, followed by inflammatory cytokine/chemokine secretion. This promotes tumour immune infiltration, innate and adaptive immune cell activation and T cell priming, culminating in targeted tumour cell killing, i.e., an immunologically ‘cold’ tumour microenvironment is transformed into a ‘hot’ tumour. However, as with all immunotherapies, not all patients respond in a uniformly favourable manner. Our study herein, shows a differential immune response by patients to intravenous Pexa-Vec therapy, whereby some patients responded to the virus in a typical and expected manner, demonstrating a significant IFN induction and subsequent peripheral immune activation. However, other patients experienced a markedly subdued immune response and appeared to exhibit an exhausted phenotype at baseline, characterised by higher baseline immune checkpoint expression and regulatory T cell (Treg) levels. This differential baseline immunological profile accurately predicted the subsequent response to Pexa-Vec and may, therefore, enable the development of predictive biomarkers for Pexa-Vec and OV therapies more widely. If confirmed in larger clinical trials, these immunological biomarkers may enable a personalised approach, whereby patients with an exhausted baseline immune profile are treated with immune checkpoint blockade, with the aim of reversing immune exhaustion, prior to or alongside OV therapy. MDPI 2022-04-27 /pmc/articles/PMC9103071/ /pubmed/35565310 http://dx.doi.org/10.3390/cancers14092181 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article West, Emma J. Scott, Karen J. Tidswell, Emma Bendjama, Kaidre Stojkowitz, Nicolas Lusky, Monika Kurzawa, Marta Prasad, Raj Toogood, Giles Ralph, Christy Anthoney, D. Alan Melcher, Alan A. Collinson, Fiona J. Samson, Adel Intravenous Oncolytic Vaccinia Virus Therapy Results in a Differential Immune Response between Cancer Patients |
title | Intravenous Oncolytic Vaccinia Virus Therapy Results in a Differential Immune Response between Cancer Patients |
title_full | Intravenous Oncolytic Vaccinia Virus Therapy Results in a Differential Immune Response between Cancer Patients |
title_fullStr | Intravenous Oncolytic Vaccinia Virus Therapy Results in a Differential Immune Response between Cancer Patients |
title_full_unstemmed | Intravenous Oncolytic Vaccinia Virus Therapy Results in a Differential Immune Response between Cancer Patients |
title_short | Intravenous Oncolytic Vaccinia Virus Therapy Results in a Differential Immune Response between Cancer Patients |
title_sort | intravenous oncolytic vaccinia virus therapy results in a differential immune response between cancer patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103071/ https://www.ncbi.nlm.nih.gov/pubmed/35565310 http://dx.doi.org/10.3390/cancers14092181 |
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