Additive Cytotoxic Effect of Bortezomib in Combination With anti-CD20 or anti-CD52 Monoclonal Antibodies on Chronic Lymphocytic Leukemia Cells

Leuk Res. 2006 Dec;30(12):1521-9. doi: 10.1016/j.leukres.2006.03.005. Epub 2006 Apr 19.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alemtuzumab
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antibodies, Neoplasm / pharmacology*
  • Apoptosis Regulatory Proteins / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Boronic Acids / pharmacology*
  • Bortezomib
  • Caspase 3 / drug effects
  • Caspase 3 / metabolism
  • Cell Death / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
  • Leukocytes, Mononuclear / drug effects
  • Male
  • Middle Aged
  • Pyrazines / pharmacology*
  • Rituximab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antibodies, Neoplasm
  • Apoptosis Regulatory Proteins
  • Boronic Acids
  • Pyrazines
  • Alemtuzumab
  • Rituximab
  • Bortezomib
  • Caspase 3