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Tetraspanin 8 (TSPAN 8) as a potential target for radio-immunotherapy of colorectal cancer
Tetraspanin 8 (TSPAN8) overexpression is correlated with poor prognosis in human colorectal cancer (CRC). A murine mAb Ts29.2 specific for human TSPAN8 provided significant efficiency for immunotherapy in CRC pre-clinical models. We therefore evaluate the feasability of targeting TSPAN8 in CRC with...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400644/ https://www.ncbi.nlm.nih.gov/pubmed/28423546 http://dx.doi.org/10.18632/oncotarget.15787 |
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author | Maisonial-Besset, Aurelie Witkowski, Tiffany Navarro-Teulon, Isabelle Berthier-Vergnes, Odile Fois, Giovanna Zhu, Yingying Besse, Sophie Bawa, Olivia Briat, Arnaud Quintana, Mercedes Pichard, Alexandre Bonnet, Mathilde Rubinstein, Eric Pouget, Jean-Pierre Opolon, Paule Maigne, Lydia Miot-Noirault, Elisabeth Chezal, Jean-Michel Boucheix, Claude Degoul, Françoise |
author_facet | Maisonial-Besset, Aurelie Witkowski, Tiffany Navarro-Teulon, Isabelle Berthier-Vergnes, Odile Fois, Giovanna Zhu, Yingying Besse, Sophie Bawa, Olivia Briat, Arnaud Quintana, Mercedes Pichard, Alexandre Bonnet, Mathilde Rubinstein, Eric Pouget, Jean-Pierre Opolon, Paule Maigne, Lydia Miot-Noirault, Elisabeth Chezal, Jean-Michel Boucheix, Claude Degoul, Françoise |
author_sort | Maisonial-Besset, Aurelie |
collection | PubMed |
description | Tetraspanin 8 (TSPAN8) overexpression is correlated with poor prognosis in human colorectal cancer (CRC). A murine mAb Ts29.2 specific for human TSPAN8 provided significant efficiency for immunotherapy in CRC pre-clinical models. We therefore evaluate the feasability of targeting TSPAN8 in CRC with radiolabeled Ts29.2. Staining of tissue micro-arrays with Ts29.2 revealed that TSPAN8 espression was restricted to a few human healthy tissues. DOTA-Ts29.2 was radiolabeled with (111)In or (177)Lu with radiochemical purities >95%, specific activity ranging from 300 to 600 MBq/mg, and radioimmunoreactive fractions >80%. The biodistribution of [(111)In]DOTA-Ts29.2 in nude mice bearing HT29 or SW480 CRC xenografts showed a high specificity of tumor localization with high tumor/blood ratios (HT29: 4.3; SW480-TSPAN8: 3.9 at 72h and 120h post injection respectively). Tumor-specific absorbed dose calculations for [(177)Lu]DOTA-Ts29.2 was 1.89 Gy/MBq, establishing the feasibility of using radioimmunotherapy of CRC with this radiolabeled antibody. A significant inhibition of tumor growth in HT29 tumor-bearing mice treated with [(177)Lu]DOTA-Ts29.2 was observed compared to control groups. Ex vivo experiments revealed specific DNA double strand breaks associated with cell apoptosis in [(177)Lu]DOTA-Ts29.2 treated tumors compared to controls. Overall, we provide a proof-of-concept for the use of [(111)In/(177)Lu]DOTA-Ts29.2 that specifically target in vivo aggressive TSPAN8-positive cells in CRC. |
format | Online Article Text |
id | pubmed-5400644 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-54006442017-05-03 Tetraspanin 8 (TSPAN 8) as a potential target for radio-immunotherapy of colorectal cancer Maisonial-Besset, Aurelie Witkowski, Tiffany Navarro-Teulon, Isabelle Berthier-Vergnes, Odile Fois, Giovanna Zhu, Yingying Besse, Sophie Bawa, Olivia Briat, Arnaud Quintana, Mercedes Pichard, Alexandre Bonnet, Mathilde Rubinstein, Eric Pouget, Jean-Pierre Opolon, Paule Maigne, Lydia Miot-Noirault, Elisabeth Chezal, Jean-Michel Boucheix, Claude Degoul, Françoise Oncotarget Research Paper Tetraspanin 8 (TSPAN8) overexpression is correlated with poor prognosis in human colorectal cancer (CRC). A murine mAb Ts29.2 specific for human TSPAN8 provided significant efficiency for immunotherapy in CRC pre-clinical models. We therefore evaluate the feasability of targeting TSPAN8 in CRC with radiolabeled Ts29.2. Staining of tissue micro-arrays with Ts29.2 revealed that TSPAN8 espression was restricted to a few human healthy tissues. DOTA-Ts29.2 was radiolabeled with (111)In or (177)Lu with radiochemical purities >95%, specific activity ranging from 300 to 600 MBq/mg, and radioimmunoreactive fractions >80%. The biodistribution of [(111)In]DOTA-Ts29.2 in nude mice bearing HT29 or SW480 CRC xenografts showed a high specificity of tumor localization with high tumor/blood ratios (HT29: 4.3; SW480-TSPAN8: 3.9 at 72h and 120h post injection respectively). Tumor-specific absorbed dose calculations for [(177)Lu]DOTA-Ts29.2 was 1.89 Gy/MBq, establishing the feasibility of using radioimmunotherapy of CRC with this radiolabeled antibody. A significant inhibition of tumor growth in HT29 tumor-bearing mice treated with [(177)Lu]DOTA-Ts29.2 was observed compared to control groups. Ex vivo experiments revealed specific DNA double strand breaks associated with cell apoptosis in [(177)Lu]DOTA-Ts29.2 treated tumors compared to controls. Overall, we provide a proof-of-concept for the use of [(111)In/(177)Lu]DOTA-Ts29.2 that specifically target in vivo aggressive TSPAN8-positive cells in CRC. Impact Journals LLC 2017-02-28 /pmc/articles/PMC5400644/ /pubmed/28423546 http://dx.doi.org/10.18632/oncotarget.15787 Text en Copyright: © 2017 Besset 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 Maisonial-Besset, Aurelie Witkowski, Tiffany Navarro-Teulon, Isabelle Berthier-Vergnes, Odile Fois, Giovanna Zhu, Yingying Besse, Sophie Bawa, Olivia Briat, Arnaud Quintana, Mercedes Pichard, Alexandre Bonnet, Mathilde Rubinstein, Eric Pouget, Jean-Pierre Opolon, Paule Maigne, Lydia Miot-Noirault, Elisabeth Chezal, Jean-Michel Boucheix, Claude Degoul, Françoise Tetraspanin 8 (TSPAN 8) as a potential target for radio-immunotherapy of colorectal cancer |
title | Tetraspanin 8 (TSPAN 8) as a potential target for radio-immunotherapy of colorectal cancer |
title_full | Tetraspanin 8 (TSPAN 8) as a potential target for radio-immunotherapy of colorectal cancer |
title_fullStr | Tetraspanin 8 (TSPAN 8) as a potential target for radio-immunotherapy of colorectal cancer |
title_full_unstemmed | Tetraspanin 8 (TSPAN 8) as a potential target for radio-immunotherapy of colorectal cancer |
title_short | Tetraspanin 8 (TSPAN 8) as a potential target for radio-immunotherapy of colorectal cancer |
title_sort | tetraspanin 8 (tspan 8) as a potential target for radio-immunotherapy of colorectal cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400644/ https://www.ncbi.nlm.nih.gov/pubmed/28423546 http://dx.doi.org/10.18632/oncotarget.15787 |
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