Anti-CCR7 monoclonal antibodies as a novel tool for the treatment of chronic lymphocyte leukemia

Journal of Leukocyte Biology

Cecilia Muñoz¹  Nuria E. Quintana¹  Sonia López-Giral¹  Manuel Alfonso-Pérez¹  Javier Loscertales²  Patricia Martín-Jiménez³ 

[1]Departments of Immunology and Departments of Immunology and Departments of Immunology and

[2]Hematology, Hospital Universitario de La Princesa, Madrid, Spain

[3] and Hematology, Hospital Universitario de La Princesa, Madrid, Spain

[4] and Hematology, Hospital Universitario de La Princesa, Madrid, Spain

[5] and

[6]Department of Hematology, Hospital Clínico Universitario de Salamanca, Spain Department of Hematology, Hospital Clínico Universitario de Salamanca, Spain Department of Hematology, Hospital Clínico Universitario de Salamanca, Spain

关键词: immunotherapy;    chemokines;    cytotoxicity;    metastasis;    chemotaxis;    tumor;   

DOI  :  10.1189/jlb.1105623

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

To date, chronic lymphocytic leukemia (CLL) remains incurable with current treatments, which include the monoclonal antibodies (mAbs) rituximab and alemtuzumab. The efficacy of rituximab is modest when used as single agent, and alemtuzumab induces severe immunosuppression. To develop more potent and specific therapies, we propose the CC chemokine receptor 7 (CCR7) as an attractive target molecule to treat CLL, as it not only fulfills the requirements of a high-surface expression and a good level of tissue specificity, but it also plays a crucial role in mediating the migration of the tumor cells to lymph nodes (LNs) and thus, in the development of clinical lymphadenopathy. In the current work, murine anti-human CCR7 mAb mediated a potent, complement-dependent cytotoxicity (CDC) against CLL cells while sparing normal T lymphocytes from the same patients. The sensitivity to CDC was related to the antigenic density of CCR7. Moreover, these mAb blocked the in vitro migration of CLL cells in response to CC chemokine ligand 19 (CC219), one of the physiological ligands of CCR7. Conversely, CLL cells were poorly lysed through antibody-dependent, cell-mediated cytotoxicity (ADCC), probably as a result of the murine origin and the isotype of the anti-CCR7 mAb used. Molecular engineering techniques will allow us to obtain chimeric or humanized anti-CCR7 mAb to reach the best clinical response for this common and yet incurable leukemia.

【 授权许可】

Unknown