CCR7 as a novel therapeutic target in t-cell PROLYMPHOCYTIC leukemia
T-cell prolymphocytic leukemia (T-PLL) is a poor prognostic disease with very limited options of efficient therapies. Most patients are refractory to chemotherapies and despite high response rates after alemtuzumab, virtually all patients relapse. Therefore, there is an unmet medical need for novel...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/235552 |
| Acceso en línea: | http://hdl.handle.net/10261/235552 |
| Access Level: | acceso abierto |
| Palabra clave: | CCR7 T-PLL mAb T-cell lymphomas Immunotherapy |
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CCR7 as a novel therapeutic target in t-cell PROLYMPHOCYTIC leukemiaCuesta-Mateos, CarlosFuentes, PatriciaSchrader, AlexandraJuárez-Sánchez, RaquelLoscertales, JavierMateu-Alberoa, TamaraVega-Piris, LorenaEspartero-Santos, MarinaMarcos-Jiménez, AnaSánchez-López, Blanca A.Pérez-García, YaizaJungherz, DennisOberbeckmann, SebastianWahnshaffe, LinusAndersson, Emma I.Mustjoki, SatuFaber, EdgarUrzainqui, AnaFresno, ManuelStamatakis, KonstantinosAlfranca, ArántzazuTerrón, FernandoHerling, MarcoToribio, María LuisaMuñoz-Calleja, CeciliaCCR7T-PLLmAbT-cell lymphomasImmunotherapyT-cell prolymphocytic leukemia (T-PLL) is a poor prognostic disease with very limited options of efficient therapies. Most patients are refractory to chemotherapies and despite high response rates after alemtuzumab, virtually all patients relapse. Therefore, there is an unmet medical need for novel therapies in T-PLL. As the chemokine receptor CCR7 is a molecule expressed in a wide range of malignancies and relevant in many tumor processes, the present study addressed the biologic role of this receptor in T-PLL. Furthermore, we elucidated the mechanisms of action mediated by an anti-CCR7 monoclonal antibody (mAb) and evaluated whether its anti-tumor activity would warrant development towards clinical applications in T-PLL. Our results demonstrate that CCR7 is a prognostic biomarker for overall survival in T-PLL patients and a functional receptor involved in the migration, invasion, and survival of leukemic cells. Targeting CCR7 with a mAb inhibited ligand-mediated signaling pathways and induced tumor cell killing in primary samples. In addition, directing antibodies against CCR7 was highly effective in T-cell leukemia xenograft models. Together, these findings make CCR7 an attractive molecule for novel mAb-based therapeutic applications in T-PLL, a disease where recent drug screen efforts and studies addressing new compounds have focused on chemotherapy or small molecules.(Ministerio de Economía y Competitividad, Spain). MH was funded by the German Research Foundation (DFG; HE3553/4–2) as part of the collaborative research group on mature T-cell lymphomas, “CONTROL-T” (FOR1961). The José Carreras Leukemia Foundation (03F/2016), the Köln Fortune Program, and the Fritz Thyssen foundation (10.15.2.034MN) supported MH and AS. The Köln Fortune Program also supported LW. SM was supported by the Finnish Cancer Organizations, the Finnish Cancer Institute, Academy of Finland and the Sigrid Juselius FoundationBioMed CentralConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120202021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/235552reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1186/s40364-020-00234-zSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2355522026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
CCR7 as a novel therapeutic target in t-cell PROLYMPHOCYTIC leukemia |
| title |
CCR7 as a novel therapeutic target in t-cell PROLYMPHOCYTIC leukemia |
| spellingShingle |
CCR7 as a novel therapeutic target in t-cell PROLYMPHOCYTIC leukemia Cuesta-Mateos, Carlos CCR7 T-PLL mAb T-cell lymphomas Immunotherapy |
| title_short |
CCR7 as a novel therapeutic target in t-cell PROLYMPHOCYTIC leukemia |
| title_full |
CCR7 as a novel therapeutic target in t-cell PROLYMPHOCYTIC leukemia |
| title_fullStr |
CCR7 as a novel therapeutic target in t-cell PROLYMPHOCYTIC leukemia |
| title_full_unstemmed |
CCR7 as a novel therapeutic target in t-cell PROLYMPHOCYTIC leukemia |
| title_sort |
CCR7 as a novel therapeutic target in t-cell PROLYMPHOCYTIC leukemia |
| dc.creator.none.fl_str_mv |
Cuesta-Mateos, Carlos Fuentes, Patricia Schrader, Alexandra Juárez-Sánchez, Raquel Loscertales, Javier Mateu-Alberoa, Tamara Vega-Piris, Lorena Espartero-Santos, Marina Marcos-Jiménez, Ana Sánchez-López, Blanca A. Pérez-García, Yaiza Jungherz, Dennis Oberbeckmann, Sebastian Wahnshaffe, Linus Andersson, Emma I. Mustjoki, Satu Faber, Edgar Urzainqui, Ana Fresno, Manuel Stamatakis, Konstantinos Alfranca, Arántzazu Terrón, Fernando Herling, Marco Toribio, María Luisa Muñoz-Calleja, Cecilia |
| author |
Cuesta-Mateos, Carlos |
| author_facet |
Cuesta-Mateos, Carlos Fuentes, Patricia Schrader, Alexandra Juárez-Sánchez, Raquel Loscertales, Javier Mateu-Alberoa, Tamara Vega-Piris, Lorena Espartero-Santos, Marina Marcos-Jiménez, Ana Sánchez-López, Blanca A. Pérez-García, Yaiza Jungherz, Dennis Oberbeckmann, Sebastian Wahnshaffe, Linus Andersson, Emma I. Mustjoki, Satu Faber, Edgar Urzainqui, Ana Fresno, Manuel Stamatakis, Konstantinos Alfranca, Arántzazu Terrón, Fernando Herling, Marco Toribio, María Luisa Muñoz-Calleja, Cecilia |
| author_role |
author |
| author2 |
Fuentes, Patricia Schrader, Alexandra Juárez-Sánchez, Raquel Loscertales, Javier Mateu-Alberoa, Tamara Vega-Piris, Lorena Espartero-Santos, Marina Marcos-Jiménez, Ana Sánchez-López, Blanca A. Pérez-García, Yaiza Jungherz, Dennis Oberbeckmann, Sebastian Wahnshaffe, Linus Andersson, Emma I. Mustjoki, Satu Faber, Edgar Urzainqui, Ana Fresno, Manuel Stamatakis, Konstantinos Alfranca, Arántzazu Terrón, Fernando Herling, Marco Toribio, María Luisa Muñoz-Calleja, Cecilia |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
CCR7 T-PLL mAb T-cell lymphomas Immunotherapy |
| topic |
CCR7 T-PLL mAb T-cell lymphomas Immunotherapy |
| description |
T-cell prolymphocytic leukemia (T-PLL) is a poor prognostic disease with very limited options of efficient therapies. Most patients are refractory to chemotherapies and despite high response rates after alemtuzumab, virtually all patients relapse. Therefore, there is an unmet medical need for novel therapies in T-PLL. As the chemokine receptor CCR7 is a molecule expressed in a wide range of malignancies and relevant in many tumor processes, the present study addressed the biologic role of this receptor in T-PLL. Furthermore, we elucidated the mechanisms of action mediated by an anti-CCR7 monoclonal antibody (mAb) and evaluated whether its anti-tumor activity would warrant development towards clinical applications in T-PLL. Our results demonstrate that CCR7 is a prognostic biomarker for overall survival in T-PLL patients and a functional receptor involved in the migration, invasion, and survival of leukemic cells. Targeting CCR7 with a mAb inhibited ligand-mediated signaling pathways and induced tumor cell killing in primary samples. In addition, directing antibodies against CCR7 was highly effective in T-cell leukemia xenograft models. Together, these findings make CCR7 an attractive molecule for novel mAb-based therapeutic applications in T-PLL, a disease where recent drug screen efforts and studies addressing new compounds have focused on chemotherapy or small molecules. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2021 2021 2021 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10261/235552 |
| url |
http://hdl.handle.net/10261/235552 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
http://dx.doi.org/10.1186/s40364-020-00234-z Sí |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
BioMed Central |
| publisher.none.fl_str_mv |
BioMed Central |
| dc.source.none.fl_str_mv |
reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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1869406972772614144 |
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15.198674 |