Published online before print April 7, 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Departments of Immunology and
Hematology, Hospital Universitario de La Princesa, Madrid, Spain; and
Department of Hematology, Hospital Clínico Universitario de Salamanca, Spain
1Correspondence: Servicio de Inmunología, Hospital Universitario de La Princesa, C/Diego de León 62, 28006 Madrid, Spain. E-mail: cmunoz.hlpr{at}salud.madrid.org
ABSTRACT
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.
Key Words: immunotherapy • chemokines • cytotoxicity • metastasis • chemotaxis • tumor
This article has been cited by other articles:
 |
|
 |
|
  M. Borge, P. R. Nannini, J. G. Galletti, P. E. Morande, J. S. Avalos, R. F. Bezares, M. Giordano, and R. Gamberale CXCL12-induced chemotaxis is impaired in T cells from patients with ZAP-70-negative chronic lymphocytic leukemia Haematologica, May 1, 2010; 95(5): 768 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Picchio, E. Scala, D. Pomponi, E. Caprini, M. Frontani, I. Angelucci, A. Mangoni, C. Lazzeri, M. Perez, D. Remotti, et al. CXCL13 Is Highly Produced by Sezary Cells and Enhances Their Migratory Ability via a Synergistic Mechanism Involving CCL19 and CCL21 Chemokines Cancer Res., September 1, 2008; 68(17): 7137 - 7146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Redondo-Munoz, M. Jose Terol, J. A. Garcia-Marco, and A. Garcia-Pardo Matrix metalloproteinase-9 is up-regulated by CCL21/CCR7 interaction via extracellular signal-regulated kinase-1/2 signaling and is involved in CCL21-driven B-cell chronic lymphocytic leukemia cell invasion and migration Blood, January 1, 2008; 111(1): 383 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ziegler, M. Oberbarnscheidt, S. Bulfone-Paus, R. Forster, U. Kunzendorf, and S. Krautwald CCR7 Signaling Inhibits T Cell Proliferation J. Immunol., November 15, 2007; 179(10): 6485 - 6493. [Abstract] [Full Text] [PDF]
|
|
