Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/112024
Title: A combination of an anti-SLAMF6 antibody and ibrutinib efficiently abrogates expansion of chronic lymphocytic leukemia cells
Author: Yigit, Burcu
Halibozeck, Peter J.
Chen, Shih-Shih
O'Keeffe, Michael S.
Arnason, Jon
Avigan, David
Gattei, Valter
Chiorazzi, Nicholas
Wang, Ninghai
Engel Rocamora, Pablo
Terhorst, Cox
Keywords: Leucèmia limfocítica crònica
Limfomes
Medicaments
Chronic lymphocytic leukemia
Lymphomas
Drugs
Issue Date: 25-Mar-2016
Publisher: Impact Journals
Abstract: The signaling lymphocyte activation molecule family [SLAMF] of cell surface receptors partakes in both the development of several immunocyte lineages and innate and adaptive immune responses in humans and mice. For instance, the homophilic molecule SLAMF6 (CD352) is in part involved in natural killer T cell development, but also modulates T follicular helper cell and germinal B cell interactions. Here we report that upon transplantation of a well-defined aggressive murine B220+CD5+ Chronic Lymphocytic Leukemia (CLL) cell clone, TCL1-192, into SCID mice one injection of a monoclonal antibody directed against SLAMF6 (αSlamf6) abrogates tumor progression in the spleen, bone marrow and blood. Similarly, progression of a murine B cell lymphoma, LMP2A/λMyc, was also eliminated by αSlamf6. But, surprisingly, αSLAMF6 neither eliminated TCL1-192 nor LMP2A/λMyc cells, which resided in the peritoneal cavity or omentum. This appeared to be dependent upon the tumor environment, which affected the frequency of sub-populations of the TCL1-192 clone or the inability of peritoneal macrophages to induce Antibody Dependent Cellular Cytotoxicity (ADCC). However, co-administering αSlamf6 with the Bruton tyrosine kinase (Btk) inhibitor, ibrutinib, synergized to efficiently eliminate the tumor cells in the spleen, bone marrow, liver and the peritoneal cavity. Because an anti-human SLAMF6 mAb efficiently killed human CLL cells in vitro and in vivo, we propose that a combination of αSlamf6 with ibrutinib should be considered as a novel therapeutic approach for CLL and other B cell tumors.
Note: Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.8378
It is part of: Oncotarget, 2016, vol. 7, p. 26346-26360
Related resource: https://doi.org/10.18632/oncotarget.8378
URI: http://hdl.handle.net/2445/112024
ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (Biomedicina)

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