In:
British Journal of Haematology, Wiley, Vol. 144, No. 6 ( 2009-03), p. 848-855
Abstract:
Antibody‐based therapies, such as rituximab and alemtuzumab, have contributed significantly to the treatment of Chronic Lymphocytic leukaemia (CLL). The CD40 antigen is expressed predominantly on B‐cells and represents a potential target for immune‐based therapies. SGN‐40 is a humanized IgG1 monoclonal antibody currently in Phase I/II clinical trials for indolent lymphomas, diffuse large B cell lymphomas and Multiple Myeloma. Its biological effect on CLL cells has not been studied. The present study demonstrated that SGN‐40 mediated modest apoptosis in a subset of patients with secondary cross‐linking but did not mediate complement‐dependent cytotoxicity. SGN‐40 also mediated antibody‐dependent cellular cytotoxicity (ADCC) predominantly through natural killer (NK) cells. Previous studies by our group and others have demonstrated that lenalidomide upregulates CD40 expression on primary B CLL cells and activates NK‐cells. We therefore examined for the combinatorial effect of lenalidomide and SGN‐40 and demonstrated that both enhanced direct apoptosis and ADCC against primary CLL B cells. These data together provide justification for clinical trials of SGN‐40 and lenalidomide in combination for CLL therapy.
Type of Medium:
Online Resource
ISSN:
0007-1048
,
1365-2141
DOI:
10.1111/bjh.2009.144.issue-6
DOI:
10.1111/j.1365-2141.2008.07548.x
Language:
English
Publisher:
Wiley
Publication Date:
2009
detail.hit.zdb_id:
1475751-5
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