Anti-CCR7 therapy exerts a potent anti-tumor activity in a xenograft model of human mantle cell lymphoma
Entity
UAM. Departamento de MedicinaPublisher
BioMed CentralDate
2013-12-04Citation
10.1186/1756-8722-6-89
Journal of Hematology & Oncology 6.1 (2013): 89
ISSN
1756-8722 (online)DOI
10.1186/1756-8722-6-89Funded by
BSC is supported by the Fundación Leucemia Linfoma and Fundación Vistare. Grants from the Fondo de Investigaciones Sanitarias to CMC (PI09/01336 and PI12/00494), JMZ (PI12/01135) and EFR (PI11/00128) and from IMMED to CMC supported this workEditor's Version
http://www.jhoonline.org/content/6/1/89Subjects
Apoptosis; Animal; Lymphoma; Inbred NOD; CCR7; Xenograft Model Antitumor Assays; MedicinaRights
© 2013 Somovilla-Crespo et al.Abstract
Background: The chemokine receptor CCR7 mediates lymphoid dissemination of many cancers, including lymphomas and epithelial carcinomas, thus representing an attractive therapeutic target. Previous results have highlighted the potential of the anti-CCR7 monoclonal antibodies to inhibit migration in transwell assays. The present study aimed to evaluate the in vivo therapeutic efficacy of an anti-CCR7 antibody in a xenografted human mantle cell lymphoma model. Methods. NOD/SCID mice were either subcutaneously or intravenously inoculated with Granta-519 cells, a human cell line derived from a leukemic mantle cell lymphoma. The anti-CCR7 mAb treatment (3 × 200 μg) was started on day 2 or 7 to target lymphoma cells in either a peri-implantation or a post-implantation stage, respectively. Results: The anti-CCR7 therapy significantly delayed the tumor appearance and also reduced the volumes of tumors in the subcutaneous model. Moreover, an increased number of apoptotic tumor cells was detected in mice treated with the anti-CCR7 mAb compared to the untreated animals. In addition, significantly reduced number of Granta-519 cells migrated from subcutaneous tumors to distant lymphoid organs, such as bone marrow and spleen in the anti-CCR7 treated mice. In the intravenous models, the anti-CCR7 mAb drastically increased survival of the mice. Accordingly, dissemination and infiltration of tumor cells in lymphoid and non-lymphoid organs, including lungs and central nervous system, was almost abrogated. Conclusions: The anti-CCR7 mAb exerts a potent anti-tumor activity and might represent an interesting therapeutic alternative to conventional therapies
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Google Scholar:Somovilla-Crespo, Beatriz
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Alfonso-Pérez, Manuel J.
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Cuesta-Mateos, Carlos
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Carballo-De Dios, Cristina
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Beltrán, Amada Elia
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Terrón, Fernando
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Pérez-Villar, Juan José
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Gamallo-Amat, Carlos
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Pérez-Chacón, Gema
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Fernández Ruiz, Elena
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Zapata, Juán M.
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Muñoz Calleja, Cecilia
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