A combination of an anti-SLAMF6 antibody and ibrutinib efficiently abrogates expansion of chronic lymphocytic leukemia cells

Burcu Yigit, Peter J. Halibozek, Shih Shih Chen, Michael S. O'Keeffe, Jon Arnason, David Avigan, Valter Gattei, Atul Bhan, Osman Cen, Richard Longnecker, Nicholas Chiorazzi, Ninghai Wang, Pablo Engel, Cox Terhorst

Research output: Contribution to journalArticle

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 (aSlamf6) abrogates tumor progression in the spleen, bone marrow and blood. Similarly, progression of a murine B cell lymphoma, LMP2A/lMyc, was also eliminated by aSlamf6. But, surprisingly, aSLAMF6 neither eliminated TCL1-192 nor LMP2A/lMyc 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 aSlamf6 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 aSlamf6 with ibrutinib should be considered as a novel therapeutic approach for CLL and other B cell tumors.

Original languageEnglish
Pages (from-to)26346-26360
Number of pages15
JournalOncotarget
Volume7
Issue number18
DOIs
Publication statusPublished - May 1 2016

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Keywords

  • BCR
  • CLL
  • Ibrutinib
  • SLAMF6
  • TCL1-192

ASJC Scopus subject areas

  • Oncology

Cite this

Yigit, B., Halibozek, P. J., Chen, S. S., O'Keeffe, M. S., Arnason, J., Avigan, D., Gattei, V., Bhan, A., Cen, O., Longnecker, R., Chiorazzi, N., Wang, N., Engel, P., & Terhorst, C. (2016). A combination of an anti-SLAMF6 antibody and ibrutinib efficiently abrogates expansion of chronic lymphocytic leukemia cells. Oncotarget, 7(18), 26346-26360. https://doi.org/10.18632/oncotarget.8378