Efficacy of coxsackievirus A21 against drug-resistant neoplastic B cells
Primary drug resistance and minimal residual disease are major challenges in the treatment of B cell neoplasms. Therefore, this study aimed to identify a novel treatment capable of eradicating malignant B cells and drug-resistant disease. Oncolytic viruses eradicate malignant cells by direct oncolys...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-06-01
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| Series: | Molecular Therapy: Oncolytics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770523000244 |
| _version_ | 1827970142567399424 |
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| author | Matthew Holmes Gina B. Scott Samuel Heaton Tyler Barr Basem Askar Louise M.E. Müller Victoria A. Jennings Christy Ralph Cathy Burton Alan Melcher Peter Hillmen Christopher Parrish Fiona Errington-Mais |
| author_facet | Matthew Holmes Gina B. Scott Samuel Heaton Tyler Barr Basem Askar Louise M.E. Müller Victoria A. Jennings Christy Ralph Cathy Burton Alan Melcher Peter Hillmen Christopher Parrish Fiona Errington-Mais |
| author_sort | Matthew Holmes |
| collection | DOAJ |
| description | Primary drug resistance and minimal residual disease are major challenges in the treatment of B cell neoplasms. Therefore, this study aimed to identify a novel treatment capable of eradicating malignant B cells and drug-resistant disease. Oncolytic viruses eradicate malignant cells by direct oncolysis and activation of anti-tumor immunity, have proven anti-cancer efficacy, and are safe and well tolerated in clinical use. Here, we demonstrate that the oncolytic virus coxsackievirus A21 can kill a range of B cell neoplasms, irrespective of an anti-viral interferon response. Moreover, CVA21 retained its capacity to kill drug-resistant B cell neoplasms, where drug resistance was induced by co-culture with tumor microenvironment support. In some cases, CVA21 efficacy was actually enhanced, in accordance with increased expression of the viral entry receptor ICAM-1. Importantly, the data confirmed preferential killing of malignant B cells and CVA21 dependence on oncogenic B cell signaling pathways. Significantly, CVA21 also activated natural killer (NK) cells to kill neoplastic B cells and drug-resistant B cells remained susceptible to NK cell-mediated lysis. Overall, these data reveal a dual mode of action of CVA21 against drug-resistant B cells and support the development of CVA21 for the treatment of B cell neoplasms. |
| first_indexed | 2024-04-09T18:49:25Z |
| format | Article |
| id | doaj.art-5203c050e9894f55a9405ad6fce9ab42 |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-04-09T18:49:25Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-5203c050e9894f55a9405ad6fce9ab422023-04-10T04:04:03ZengElsevierMolecular Therapy: Oncolytics2372-77052023-06-01291729Efficacy of coxsackievirus A21 against drug-resistant neoplastic B cellsMatthew Holmes0Gina B. Scott1Samuel Heaton2Tyler Barr3Basem Askar4Louise M.E. Müller5Victoria A. Jennings6Christy Ralph7Cathy Burton8Alan Melcher9Peter Hillmen10Christopher Parrish11Fiona Errington-Mais12Leeds Institute of Medical Research, University of Leeds, Beckett Street, Leeds LS9 7TF, UKLeeds Institute of Medical Research, University of Leeds, Beckett Street, Leeds LS9 7TF, UKLeeds Institute of Medical Research, University of Leeds, Beckett Street, Leeds LS9 7TF, UKLeeds Institute of Medical Research, University of Leeds, Beckett Street, Leeds LS9 7TF, UKLeeds Institute of Medical Research, University of Leeds, Beckett Street, Leeds LS9 7TF, UKLeeds Institute of Medical Research, University of Leeds, Beckett Street, Leeds LS9 7TF, UKLeeds Institute of Medical Research, University of Leeds, Beckett Street, Leeds LS9 7TF, UK; The Institute of Cancer Research, Division of Radiotherapy and Imaging, Chester Beatty Laboratories, London SW3 6JB, UKLeeds Institute of Medical Research, University of Leeds, Beckett Street, Leeds LS9 7TF, UKHaematological Malignancy Diagnostic Service, Leeds Teaching Hospitals, Beckett Street, Leeds LS9 7TF, UKThe Institute of Cancer Research, Division of Radiotherapy and Imaging, Chester Beatty Laboratories, London SW3 6JB, UKLeeds Institute of Medical Research, University of Leeds, Beckett Street, Leeds LS9 7TF, UKSt James’s University Hospital, Leeds Teaching Hospital, Beckett Street, Leeds LS9 7TF, UKLeeds Institute of Medical Research, University of Leeds, Beckett Street, Leeds LS9 7TF, UK; Corresponding author: Fiona Errington-Mais, Leeds Institute of Medical Research, Wellcome Trust Brenner Building (Level 5), University of Leeds, Beckett Street, Leeds LS9 7TF, UK.Primary drug resistance and minimal residual disease are major challenges in the treatment of B cell neoplasms. Therefore, this study aimed to identify a novel treatment capable of eradicating malignant B cells and drug-resistant disease. Oncolytic viruses eradicate malignant cells by direct oncolysis and activation of anti-tumor immunity, have proven anti-cancer efficacy, and are safe and well tolerated in clinical use. Here, we demonstrate that the oncolytic virus coxsackievirus A21 can kill a range of B cell neoplasms, irrespective of an anti-viral interferon response. Moreover, CVA21 retained its capacity to kill drug-resistant B cell neoplasms, where drug resistance was induced by co-culture with tumor microenvironment support. In some cases, CVA21 efficacy was actually enhanced, in accordance with increased expression of the viral entry receptor ICAM-1. Importantly, the data confirmed preferential killing of malignant B cells and CVA21 dependence on oncogenic B cell signaling pathways. Significantly, CVA21 also activated natural killer (NK) cells to kill neoplastic B cells and drug-resistant B cells remained susceptible to NK cell-mediated lysis. Overall, these data reveal a dual mode of action of CVA21 against drug-resistant B cells and support the development of CVA21 for the treatment of B cell neoplasms.http://www.sciencedirect.com/science/article/pii/S2372770523000244B cell neoplasmdrug resistanceoncolytic viruscoxsackievirus A21tumor microenvironmentChronic Lymphocytic Leukemia |
| spellingShingle | Matthew Holmes Gina B. Scott Samuel Heaton Tyler Barr Basem Askar Louise M.E. Müller Victoria A. Jennings Christy Ralph Cathy Burton Alan Melcher Peter Hillmen Christopher Parrish Fiona Errington-Mais Efficacy of coxsackievirus A21 against drug-resistant neoplastic B cells Molecular Therapy: Oncolytics B cell neoplasm drug resistance oncolytic virus coxsackievirus A21 tumor microenvironment Chronic Lymphocytic Leukemia |
| title | Efficacy of coxsackievirus A21 against drug-resistant neoplastic B cells |
| title_full | Efficacy of coxsackievirus A21 against drug-resistant neoplastic B cells |
| title_fullStr | Efficacy of coxsackievirus A21 against drug-resistant neoplastic B cells |
| title_full_unstemmed | Efficacy of coxsackievirus A21 against drug-resistant neoplastic B cells |
| title_short | Efficacy of coxsackievirus A21 against drug-resistant neoplastic B cells |
| title_sort | efficacy of coxsackievirus a21 against drug resistant neoplastic b cells |
| topic | B cell neoplasm drug resistance oncolytic virus coxsackievirus A21 tumor microenvironment Chronic Lymphocytic Leukemia |
| url | http://www.sciencedirect.com/science/article/pii/S2372770523000244 |
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