Cancer Immunology, Immunotherapy, 2015, Vol.64(6), p.665(12)
Byline: Carlos Cuesta-Mateos (1,2), Javier Loscertales (3), Anna Kreutzman (1), Beatriz Colom-Fernandez (1), Itxaso Portero-Sainz (1), Juan Jose Perez-Villar (1), Fernando Terron (2), Cecilia Munoz-Calleja (1) Keywords: CCR7; mAb; p53; Fludarabine; CLL Abstract: Chronic lymphocytic leukemia (CLL) with deletions of the p53 locus on chromosome 17 and/or refractory to fludarabine chemoimmunotherapy remains a major clinical problem with few therapeutic options. Currently, these types of CLL are treated with approaches that do not target the p53 pathway, such as small molecules and monoclonal antibodies (mAb). We have previously postulated anti-CCR7 mAb therapy as a novel CLL treatment. In the present study, we evaluated the in vitro efficacy of anti-CCR7 mAb as a single agent in CLL patients with high-risk cytogenetics and/or refractory to fludarabine, by measuring CCR7 surface expression and complement-dependent cytotoxicity. Our results demonstrate that CCR7 is highly expressed in challenging and heavily treated CLL patients. In addition, the complement-mediated mechanism of action of this mAb effectively eradicates CLL cells while sparing subsets of T cells in these patients. Moreover, this mAb outperformed the activity of alemtuzumab, the mAb with the highest efficacy in these groups. Finally, in vitro activity was also demonstrated in patients with a disease refractory to both fludarabine and alemtuzumab, and patients harboring 11q22 deletion. Our results propose that anti-CCR7 mAb is an effective and promising future treatment in high-risk CLL. Author Affiliation: (1) Servicio de Inmunologia, Departamento de Inmunologia, Instituto de Investigacion Sanitaria Hospital Universitario de La Princesa, C/Diego de Leon 62, 28006, Madrid, Spain (2) IMMED S.L., Immunological and Medicinal Products, Madrid, Spain (3) Departamento de Hematologia, Instituto de Investigacion Sanitaria Hospital Universitario de La Princesa, Madrid, Spain Article History: Registration Date: 16/02/2015 Received Date: 16/09/2014 Accepted Date: 14/02/2015 Online Date: 28/02/2015 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00262-015-1670-z) contains supplementary material, which is available to authorized users.
Tumor Proteins – Risk Factors ; Tumor Proteins – Care and Treatment ; Chronic Lymphocytic Leukemia – Risk Factors ; Chronic Lymphocytic Leukemia – Care and Treatment