Efficacy of coxsackievirus A21 against drug-resistant neoplastic B cells.
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Embargo End Date
ICR Authors
Authors
Holmes, M
Scott, GB
Heaton, S
Barr, T
Askar, B
Müller, LME
Jennings, VA
Ralph, C
Burton, C
Melcher, A
Hillmen, P
Parrish, C
Errington-Mais, F
Scott, GB
Heaton, S
Barr, T
Askar, B
Müller, LME
Jennings, VA
Ralph, C
Burton, C
Melcher, A
Hillmen, P
Parrish, C
Errington-Mais, F
Document Type
Journal Article
Date
2023-06-15
Date Accepted
2023-03-21
Abstract
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.
Citation
Molecular Therapy: Oncolytics, 2023, 29 pp. 17 - 29
Source Title
Molecular Therapy: Oncolytics
Publisher
CELL PRESS
ISSN
2372-7705
eISSN
2372-7705
Collections
Research Team
Trans Immunotherapy