Additive cytotoxic effect of bortezomib in combination with anti-CD20 or anti-CD52 monoclonal antibodies on chronic lymphocytic leukemia cells.
Inhibitor of proteasome, bortezomib (BOR), although highly active in vitro, showed unexpectedly low efficacy in vivo in patients with B-CLL when used alone. We studied the in vitro cytotoxic effects of BOR in combination with anti-CD20 (rituximab, RIT) or anti-CD52 (campath, CAM) monoclonal antibodies on B-CLL cells. Both BOR+RIT and BOR+CAM combinations exerted additive cytotoxicity, triggering caspase-dependent apoptosis. The treatment significantly modified expression of several apoptosis-regulating proteins, including upregulation of Bax or downregulation of Bcl-2 and Mcl-1 by BOR+RIT, as well as downregulation of Bcl-2 and XIAP by BOR+CAM. These data suggest the feasibility of concomitant use of those agents for the treatment of B-CLL patients.
Smolewski
Piotr
P
Department of Hematology, Medical University of Lodz, Poland. piotr_smolewski@wp.pl
Duechler
Markus
M
Linke
Anna
A
Cebula
Barbara
B
Grzybowska-Izydorczyk
Olga
O
Shehata
Medhat
M
Robak
Tadeusz
T
D000368:Aged; D000369:Aged, 80 and over; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000494:pharmacology*; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D051017:Apoptosis Regulatory Proteins; D001897:Boronic Acids; D011719:Pyrazines; D000074323:Alemtuzumab; D000069283:Rituximab; D000069286:Bortezomib; D053148:Caspase 3