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Systemic therapy with oncolytic myxoma virus cures established residual multiple myeloma in mice
Multiple myeloma is an incurable malignancy of plasma B-cells. Traditional chemotherapeutic regimes often induce initial tumor regression; however, virtually all patients eventually succumb to relapse caused by either reintroduction of disease during autologous transplant or expansion of chemotherap...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142464/ https://www.ncbi.nlm.nih.gov/pubmed/27933316 http://dx.doi.org/10.1038/mto.2016.32 |
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author | Bartee, Eric Bartee, Mee Y Bogen, Bjarne Yu, Xue-Zhong |
author_facet | Bartee, Eric Bartee, Mee Y Bogen, Bjarne Yu, Xue-Zhong |
author_sort | Bartee, Eric |
collection | PubMed |
description | Multiple myeloma is an incurable malignancy of plasma B-cells. Traditional chemotherapeutic regimes often induce initial tumor regression; however, virtually all patients eventually succumb to relapse caused by either reintroduction of disease during autologous transplant or expansion of chemotherapy resistant minimal residual disease. It has been previously demonstrated that an oncolytic virus known as myxoma can completely prevent myeloma relapse caused by reintroduction of malignant cells during autologous transplant. The ability of this virus to treat established residual disease in vivo, however, remained unknown. Here we demonstrate that intravenous administration of myxoma virus into mice bearing disseminated myeloma results in the elimination of 70–90% of malignant cells within 24 hours. This rapid debulking was dependent on direct contact of myxoma virus with residual myeloma and did not occur through destruction of the hematopoietic bone marrow niche. Importantly, systemic myxoma therapy also induced potent antimyeloma CD8(+) T cell responses which localized to the bone marrow and were capable of completely eradicating established myeloma in some animals. These results demonstrate that oncolytic myxoma virus is not only effective at preventing relapse caused by reinfusion of tumor cells during stem cell transplant, but is also potentially curative for patients bearing established minimal residual disease. |
format | Online Article Text |
id | pubmed-5142464 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51424642016-12-08 Systemic therapy with oncolytic myxoma virus cures established residual multiple myeloma in mice Bartee, Eric Bartee, Mee Y Bogen, Bjarne Yu, Xue-Zhong Mol Ther Oncolytics Article Multiple myeloma is an incurable malignancy of plasma B-cells. Traditional chemotherapeutic regimes often induce initial tumor regression; however, virtually all patients eventually succumb to relapse caused by either reintroduction of disease during autologous transplant or expansion of chemotherapy resistant minimal residual disease. It has been previously demonstrated that an oncolytic virus known as myxoma can completely prevent myeloma relapse caused by reintroduction of malignant cells during autologous transplant. The ability of this virus to treat established residual disease in vivo, however, remained unknown. Here we demonstrate that intravenous administration of myxoma virus into mice bearing disseminated myeloma results in the elimination of 70–90% of malignant cells within 24 hours. This rapid debulking was dependent on direct contact of myxoma virus with residual myeloma and did not occur through destruction of the hematopoietic bone marrow niche. Importantly, systemic myxoma therapy also induced potent antimyeloma CD8(+) T cell responses which localized to the bone marrow and were capable of completely eradicating established myeloma in some animals. These results demonstrate that oncolytic myxoma virus is not only effective at preventing relapse caused by reinfusion of tumor cells during stem cell transplant, but is also potentially curative for patients bearing established minimal residual disease. Nature Publishing Group 2016-12-07 /pmc/articles/PMC5142464/ /pubmed/27933316 http://dx.doi.org/10.1038/mto.2016.32 Text en Copyright © 2016 Official journal of the American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Article Bartee, Eric Bartee, Mee Y Bogen, Bjarne Yu, Xue-Zhong Systemic therapy with oncolytic myxoma virus cures established residual multiple myeloma in mice |
title | Systemic therapy with oncolytic myxoma virus cures established residual multiple myeloma in mice |
title_full | Systemic therapy with oncolytic myxoma virus cures established residual multiple myeloma in mice |
title_fullStr | Systemic therapy with oncolytic myxoma virus cures established residual multiple myeloma in mice |
title_full_unstemmed | Systemic therapy with oncolytic myxoma virus cures established residual multiple myeloma in mice |
title_short | Systemic therapy with oncolytic myxoma virus cures established residual multiple myeloma in mice |
title_sort | systemic therapy with oncolytic myxoma virus cures established residual multiple myeloma in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142464/ https://www.ncbi.nlm.nih.gov/pubmed/27933316 http://dx.doi.org/10.1038/mto.2016.32 |
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