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dc.contributor.authorVela, Maria
dc.contributor.authorBueno, David
dc.contributor.authorGonzález-Navarro, Pablo
dc.contributor.authorBrito, Ariadna
dc.contributor.authorFernandez, Lucia 
dc.contributor.authorEscudero, Adela
dc.contributor.authorValentín, Jaime
dc.contributor.authorMestre-Durán, Carmen
dc.contributor.authorArranz-Álvarez, Marina
dc.contributor.authorPérez de Diego, Rebeca
dc.contributor.authorMendiola, Marta
dc.contributor.authorPozo-Kreilinger, José Juan
dc.contributor.authorPérez-Martínez, Antonio
dc.identifier.citationFront Immunol. 2019;10:1814.es_ES
dc.description.abstractSarcoma 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.es_ES
dc.description.sponsorshipThis work was supported in part by the National Health Service of Spain, Instituto de Salud Carlos III (ISCIII), FONDOS FEDER grant (FIS) PI15/00973; Asociacion Espanola Contra el Cancer to AP-M; CRIS Foundation to Beat Cancer grant to JV, LF, and AE; and Patients' Support Associations Fundacion Mari Paz Jimenez Casado and La Sonrisa de Alex to MV and the research project.es_ES
dc.publisherFrontiers Media es_ES
dc.subjectActivated and expanded natural killer (NKAE) cellses_ES
dc.subjectChemokine C-X-C receptor 4 (CXCR4)es_ES
dc.subjectTherapeutic antibodyes_ES
dc.titleAnti-CXCR4 Antibody Combined With Activated and Expanded Natural Killer Cells for Sarcoma Immunotherapyes_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderAsociación Española Contra el Cáncer 
dc.contributor.funderCRIS contra el Cáncer 
dc.contributor.funderPatients' Support Association Fundacion Mari Paz Jimenez Casado
dc.contributor.funderFundación la Sonrisa de Alex para la investigación y el tratamiento del sarcoma de Ewing 
dc.identifier.journalFrontiers in immunologyes_ES
dc.repisalud.orgCNIOCNIO::Unidades técnicas::Unidad de Investigación Clínica de Tumores Hematológicos H12O-CNIOes_ES
dc.rights.accessRightsopen accesses_ES

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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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