Variable Contribution of Monoclonal Antibodies to ADCC in patients with chronic
lymphocytic leukemia.
James Weitzman, Monica Betancur, Laurent Boissel, Arthur P Rabinowitz, Andreas
Klein, and Hans Klingemann
Leuk Lymphoma, June 26, 2009; 1-8.

Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA, USA.

Monoclonal antibodies (mAbs) are increasingly used in treatment protocols for
chronic lymphocytic leukemia (CLL). Here we determined (i) the extent of
antibody-dependent cellular cytotoxicity (ADCC) of four different mAbs against
primary CLL cells, (ii) whether ADCC correlates with antigen density on CLL
cells, and (iii) whether allogeneic natural killer (NK) cells display superior
ADCC than autologous. Effector cells for ADCC were (i) NK-92 cells not
expressing FcR, (ii) NK-92 cells transfected with a high-affinity Fc receptor,
(iii) autologous NK cells from patients with CLL, (iv) allogeneic NK cells.
Results suggest that ADCC contributes to killing of CLL cells by anti-CD20
antibodies (rituximab and veltuzumab), whereas mAbs against CD22 (epratuzumab)
and CD23 (lumiliximab) showed minimal ADCC. The magnitude of anti-CD20 mediated
ADCC did not correlate with antigen density of CD20. ADCC was not influenced by
the FcR genotype expressed by autologous NK cells. Allogeneic NK cells were
superior to autologous NK cells in killing primary CLL cells.
PMID: 19562616

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