Anti-CXCR4 antibody combined with activated and expanded natural killer cells for sarcoma immunotherapy
Sarcoma is one of the most severe forms of pediatric cancer and current therapies-chemotherapy and surgery-fail to eradicate the disease in half of patients. Preclinical studies combining new therapeutic approaches can be useful to design better therapies. On one hand, it is known that CXCR4 express...
| Autores: | , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/715620 |
| Acceso en línea: | http://hdl.handle.net/10486/715620 https://dx.doi.org/10.3389/fimmu.2019.01814 |
| Access Level: | acceso abierto |
| Palabra clave: | activated and expanded natural killer (NKAE) cells chemokine C-X-C receptor 4 (CXCR4) immunotherapy metastasis sarcoma therapeutic antibody Medicina |
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Anti-CXCR4 antibody combined with activated and expanded natural killer cells for sarcoma immunotherapyVela, MariaBueno, DavidGonzález Navarro, PabloBrito, AriadnaFernández Arroyo Camacho, LucíaEscudero, AdelaValentín, JaimeMestre-Durán, CarmenArranz Álvarez, Marinade Diego, Rebeca PérezMendiola, MartaPozo Kreilinger, José JuanPérez Martínez, Antonioactivated and expanded natural killer (NKAE) cellschemokine C-X-C receptor 4 (CXCR4)immunotherapymetastasissarcomatherapeutic antibodyMedicinaSarcoma is one of the most severe forms of pediatric cancer and current therapies-chemotherapy and surgery-fail to eradicate the disease in half of patients. Preclinical studies combining new therapeutic approaches can be useful to design better therapies. On one hand, it is known that CXCR4 expression is implicated in rhabdomyosarcoma progression, so we analyzed relapses and chemotherapy-resistant rhabdomyosarcoma tumors from pediatric patients and found that they had particularly high levels of CXCR4 expression. Moreover, in assays in vitro, anti-CXCR4 blocking antibody (MDX1338) efficiently reduced migration and invasion of alveolar rhabdomyosarcoma RH30 cells. On the other hand, activated and expanded natural killer (NKAE) cell therapy showed high cytotoxicity against sarcoma cells in vitro and completely inhibited RH30 tumor implantation in vivo. Only the combination of MDX1338 and NKAE treatments completely suppressed metastasis in mice. In this study, we propose a novel therapeutic approach based on anti-CXCR4 blocking antibody in combination with NKAE cell therapy to prevent rhabdomyosarcoma tumor implantation and lung metastasis. These results provide the first evidence for the efficacy of this combined immunotherapy for preventing sarcoma disease disseminationThis work was supported in part by the National Health Service of Spain, Instituto de Salud Carlos III (ISCIII), FONDOS FEDER grant (FIS) PI15/00973; Asociación Española Contra el Cáncer to AP-M; CRIS Foundation to Beat Cancer grant to JV, LF, and AE; and Patients’ Support Associations Fundación Mari Paz Jiménez Casado and La Sonrisa de Álex to MV and the research projectFrontiers MediaDepartamento de PediatríaFacultad de Medicina20192019-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/715620https://dx.doi.org/10.3389/fimmu.2019.01814reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7156202026-06-23T12:46:27Z |
| dc.title.none.fl_str_mv |
Anti-CXCR4 antibody combined with activated and expanded natural killer cells for sarcoma immunotherapy |
| title |
Anti-CXCR4 antibody combined with activated and expanded natural killer cells for sarcoma immunotherapy |
| spellingShingle |
Anti-CXCR4 antibody combined with activated and expanded natural killer cells for sarcoma immunotherapy Vela, Maria activated and expanded natural killer (NKAE) cells chemokine C-X-C receptor 4 (CXCR4) immunotherapy metastasis sarcoma therapeutic antibody Medicina |
| title_short |
Anti-CXCR4 antibody combined with activated and expanded natural killer cells for sarcoma immunotherapy |
| title_full |
Anti-CXCR4 antibody combined with activated and expanded natural killer cells for sarcoma immunotherapy |
| title_fullStr |
Anti-CXCR4 antibody combined with activated and expanded natural killer cells for sarcoma immunotherapy |
| title_full_unstemmed |
Anti-CXCR4 antibody combined with activated and expanded natural killer cells for sarcoma immunotherapy |
| title_sort |
Anti-CXCR4 antibody combined with activated and expanded natural killer cells for sarcoma immunotherapy |
| dc.creator.none.fl_str_mv |
Vela, Maria Bueno, David González Navarro, Pablo Brito, Ariadna Fernández Arroyo Camacho, Lucía Escudero, Adela Valentín, Jaime Mestre-Durán, Carmen Arranz Álvarez, Marina de Diego, Rebeca Pérez Mendiola, Marta Pozo Kreilinger, José Juan Pérez Martínez, Antonio |
| author |
Vela, Maria |
| author_facet |
Vela, Maria Bueno, David González Navarro, Pablo Brito, Ariadna Fernández Arroyo Camacho, Lucía Escudero, Adela Valentín, Jaime Mestre-Durán, Carmen Arranz Álvarez, Marina de Diego, Rebeca Pérez Mendiola, Marta Pozo Kreilinger, José Juan Pérez Martínez, Antonio |
| author_role |
author |
| author2 |
Bueno, David González Navarro, Pablo Brito, Ariadna Fernández Arroyo Camacho, Lucía Escudero, Adela Valentín, Jaime Mestre-Durán, Carmen Arranz Álvarez, Marina de Diego, Rebeca Pérez Mendiola, Marta Pozo Kreilinger, José Juan Pérez Martínez, Antonio |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Departamento de Pediatría Facultad de Medicina |
| dc.subject.none.fl_str_mv |
activated and expanded natural killer (NKAE) cells chemokine C-X-C receptor 4 (CXCR4) immunotherapy metastasis sarcoma therapeutic antibody Medicina |
| topic |
activated and expanded natural killer (NKAE) cells chemokine C-X-C receptor 4 (CXCR4) immunotherapy metastasis sarcoma therapeutic antibody Medicina |
| description |
Sarcoma is one of the most severe forms of pediatric cancer and current therapies-chemotherapy and surgery-fail to eradicate the disease in half of patients. Preclinical studies combining new therapeutic approaches can be useful to design better therapies. On one hand, it is known that CXCR4 expression is implicated in rhabdomyosarcoma progression, so we analyzed relapses and chemotherapy-resistant rhabdomyosarcoma tumors from pediatric patients and found that they had particularly high levels of CXCR4 expression. Moreover, in assays in vitro, anti-CXCR4 blocking antibody (MDX1338) efficiently reduced migration and invasion of alveolar rhabdomyosarcoma RH30 cells. On the other hand, activated and expanded natural killer (NKAE) cell therapy showed high cytotoxicity against sarcoma cells in vitro and completely inhibited RH30 tumor implantation in vivo. Only the combination of MDX1338 and NKAE treatments completely suppressed metastasis in mice. In this study, we propose a novel therapeutic approach based on anti-CXCR4 blocking antibody in combination with NKAE cell therapy to prevent rhabdomyosarcoma tumor implantation and lung metastasis. These results provide the first evidence for the efficacy of this combined immunotherapy for preventing sarcoma disease dissemination |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2019-01-01 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10486/715620 https://dx.doi.org/10.3389/fimmu.2019.01814 |
| url |
http://hdl.handle.net/10486/715620 https://dx.doi.org/10.3389/fimmu.2019.01814 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Frontiers Media |
| publisher.none.fl_str_mv |
Frontiers Media |
| dc.source.none.fl_str_mv |
reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid |
| instname_str |
Universidad Autónoma de Madrid |
| reponame_str |
Biblos-e Archivo. Repositorio Institucional de la UAM |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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15,81155 |