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...

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Bibliographic Details
Authors: 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
Format: article
Publication Date:2019
Country:España
Institution:Universidad Autónoma de Madrid
Repository:Biblos-e Archivo. Repositorio Institucional de la UAM
Language:English
OAI Identifier:oai:repositorio.uam.es:10486/715620
Online Access:http://hdl.handle.net/10486/715620
https://dx.doi.org/10.3389/fimmu.2019.01814
Access Level:Open access
Keyword:activated and expanded natural killer (NKAE) cells
chemokine C-X-C receptor 4 (CXCR4)
immunotherapy
metastasis
sarcoma
therapeutic antibody
Medicina
Description
Summary: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

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