title: Anti-CCR7 therapy exerts a potent anti-tumor activity in a xenograft model of human mantle cell lymphoma.
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.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Somovilla-Crespo
authors.forename: Manuel
authors.initials: M
authors.lastname: Alfonso-Pérez
authors.forename: Carlos
authors.initials: C
authors.lastname: Cuesta-Mateos
authors.forename: Cristina
authors.initials: C
authors.lastname: Carballo-de Dios
authors.forename: Amada E
authors.initials: AE
authors.lastname: Beltrán
authors.forename: Fernando
authors.initials: F
authors.lastname: Terrón
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Pérez-Villar
authors.forename: Carlos
authors.initials: C
authors.lastname: Gamallo-Amat
authors.forename: Gema
authors.initials: G
authors.lastname: Pérez-Chacón
authors.forename: Elena
authors.initials: E
authors.lastname: Fernández-Ruiz
authors.forename: Juan M
authors.initials: JM
authors.lastname: Zapata
authors.affiliation: Instituto de Investigación Sanitaria Princesa, Department of Immunology, Hospital Universitario de La Princesa, C/Diego de León 62, Madrid 28006, Spain. cmunozc@salud.madrid.org.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Muñoz-Calleja
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D054400:Receptors, CCR7 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C515370:CCR7 protein, human; D054400:Receptors, CCR7