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CD30-targeted oncolytic viruses as novel therapeutic approach against classical Hodgkin lymphoma
Classical Hodgkin lymphoma (cHL) is a hematopoietic malignancy with a characteristic cellular composition. The tumor mass is made up of infiltrated lymphocytes and other cells of hematologic origin but only very few neoplastic cells that are mainly identified by the diagnostic marker CD30. While mos...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849188/ https://www.ncbi.nlm.nih.gov/pubmed/29560124 http://dx.doi.org/10.18632/oncotarget.24191 |
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author | Hanauer, Julia D.S. Rengstl, Benjamin Kleinlützum, Dina Reul, Johanna Pfeiffer, Anett Friedel, Thorsten Schneider, Irene C. Newrzela, Sebastian Hansmann, Martin-Leo Buchholz, Christian J. Muik, Alexander |
author_facet | Hanauer, Julia D.S. Rengstl, Benjamin Kleinlützum, Dina Reul, Johanna Pfeiffer, Anett Friedel, Thorsten Schneider, Irene C. Newrzela, Sebastian Hansmann, Martin-Leo Buchholz, Christian J. Muik, Alexander |
author_sort | Hanauer, Julia D.S. |
collection | PubMed |
description | Classical Hodgkin lymphoma (cHL) is a hematopoietic malignancy with a characteristic cellular composition. The tumor mass is made up of infiltrated lymphocytes and other cells of hematologic origin but only very few neoplastic cells that are mainly identified by the diagnostic marker CD30. While most patients with early stage cHL can be cured by standard therapy, treatment options for relapsed or refractory cHL are still not sufficient, although immunotherapy-based approaches for the treatment of cHL patients have gained ground in the last decade. Here, we suggest a novel therapeutic concept based on oncolytic viruses selectively destroying the CD30(+)-positive cHL tumor cells. Relying on a recently described CD30-specific scFv we have generated CD30-targeted measles virus (MV-CD30) and vesicular stomatitis virus (VSV-CD30). For VSV-CD30 the VSV glycoprotein G reading frame was replaced by those of the CD30-targeted MV glycoproteins. Both viruses were found to be highly selective for CD30-positive cells as demonstrated by infection of co-cultures of target and non-target cells as well as through blocking infection by soluble CD30. Notably, VSV-CD30 yielded much higher titers than MV-CD30 and resulted in a more rapid and efficient killing of cultivated cHL-derived cell lines. Mouse tumor models revealed that intratumorally, as well as systemically injected VSV-CD30, infected cHL xenografts and significantly slowed down tumor growth resulting in a substantially prolonged survival of tumor-bearing mice. Taken together, the data support further preclinical testing of VSV-CD30 as novel therapeutic agent for the treatment of cHL and other CD30(+)-positive malignancies. |
format | Online Article Text |
id | pubmed-5849188 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-58491882018-03-20 CD30-targeted oncolytic viruses as novel therapeutic approach against classical Hodgkin lymphoma Hanauer, Julia D.S. Rengstl, Benjamin Kleinlützum, Dina Reul, Johanna Pfeiffer, Anett Friedel, Thorsten Schneider, Irene C. Newrzela, Sebastian Hansmann, Martin-Leo Buchholz, Christian J. Muik, Alexander Oncotarget Research Paper Classical Hodgkin lymphoma (cHL) is a hematopoietic malignancy with a characteristic cellular composition. The tumor mass is made up of infiltrated lymphocytes and other cells of hematologic origin but only very few neoplastic cells that are mainly identified by the diagnostic marker CD30. While most patients with early stage cHL can be cured by standard therapy, treatment options for relapsed or refractory cHL are still not sufficient, although immunotherapy-based approaches for the treatment of cHL patients have gained ground in the last decade. Here, we suggest a novel therapeutic concept based on oncolytic viruses selectively destroying the CD30(+)-positive cHL tumor cells. Relying on a recently described CD30-specific scFv we have generated CD30-targeted measles virus (MV-CD30) and vesicular stomatitis virus (VSV-CD30). For VSV-CD30 the VSV glycoprotein G reading frame was replaced by those of the CD30-targeted MV glycoproteins. Both viruses were found to be highly selective for CD30-positive cells as demonstrated by infection of co-cultures of target and non-target cells as well as through blocking infection by soluble CD30. Notably, VSV-CD30 yielded much higher titers than MV-CD30 and resulted in a more rapid and efficient killing of cultivated cHL-derived cell lines. Mouse tumor models revealed that intratumorally, as well as systemically injected VSV-CD30, infected cHL xenografts and significantly slowed down tumor growth resulting in a substantially prolonged survival of tumor-bearing mice. Taken together, the data support further preclinical testing of VSV-CD30 as novel therapeutic agent for the treatment of cHL and other CD30(+)-positive malignancies. Impact Journals LLC 2018-01-12 /pmc/articles/PMC5849188/ /pubmed/29560124 http://dx.doi.org/10.18632/oncotarget.24191 Text en Copyright: © 2018 Hanauer et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Hanauer, Julia D.S. Rengstl, Benjamin Kleinlützum, Dina Reul, Johanna Pfeiffer, Anett Friedel, Thorsten Schneider, Irene C. Newrzela, Sebastian Hansmann, Martin-Leo Buchholz, Christian J. Muik, Alexander CD30-targeted oncolytic viruses as novel therapeutic approach against classical Hodgkin lymphoma |
title | CD30-targeted oncolytic viruses as novel therapeutic approach against classical Hodgkin lymphoma |
title_full | CD30-targeted oncolytic viruses as novel therapeutic approach against classical Hodgkin lymphoma |
title_fullStr | CD30-targeted oncolytic viruses as novel therapeutic approach against classical Hodgkin lymphoma |
title_full_unstemmed | CD30-targeted oncolytic viruses as novel therapeutic approach against classical Hodgkin lymphoma |
title_short | CD30-targeted oncolytic viruses as novel therapeutic approach against classical Hodgkin lymphoma |
title_sort | cd30-targeted oncolytic viruses as novel therapeutic approach against classical hodgkin lymphoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849188/ https://www.ncbi.nlm.nih.gov/pubmed/29560124 http://dx.doi.org/10.18632/oncotarget.24191 |
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