Annals of Hematology

, Volume 83, Issue 10, pp 634–645

Rituximab and alemtuzumab induce a nonclassic, caspase-independent apoptotic pathway in B-lymphoid cell lines and in chronic lymphocytic leukemia cells

Original Article

Abstract

The monoclonal antibodies (MoAbs) alemtuzumab (anti-CD52) and rituximab (anti-CD20) produce objective clinical responses in patients with chronic lymphocytic leukemia (CLL). However, their mechanisms of action are not fully understood. Therefore, we investigated the mechanisms of lymphoma and CLL cell killing by two anti-CD20 antibodies (rituximab, B1) and by alemtuzumab. All antibodies induced complement-independent cell death in B-lymphoid cell lines Raji, Ramos, and Mec-1. The efficiency of cell killing was increased by the addition of human complement in Raji but not Ramos cells. Both alemtuzumab and rituximab also killed freshly isolated CLL cells, with a much stronger response for alemtuzumab (from eight of eight patients) compared to rituximab (from two of six patients). Cell morphology and Western blot analyses revealed that the antibody-induced cell death lacked some typical features of apoptosis such as chromatin condensation or poly-ADP-ribose polymerase (PARP) cleavage. Taken together, the results suggest that the tumor killing activity of these MoAbs is not only mediated by complement-mediated cytotoxicity (CDC) or antibody-dependent cytotoxicity (ADCC), but also by a nonclassic, caspase-independent apoptotic pathway.

Keywords

Chronic lymphocytic leukemia Monoclonal antibody therapy CD20 CD52 Caspase-independent apoptosis 

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Michael Stanglmaier
    • 1
    • 2
  • Simone Reis
    • 1
    • 3
  • Michael Hallek
    • 1
    • 4
    • 5
  1. 1.Clinical Cooperation Group for Gene TherapyGSF—National Institute of Health and EnvironmentMunichGermany
  2. 2.Trion ResearchPlanegg-MartinsriedGermany
  3. 3.Institut für Pathologie und RechtsmedizinUniversitätsklinikum UlmUlmGermany
  4. 4.Klinikum GroßhadernMedical Clinic IIIMunichGermany
  5. 5.GenzentrumUniversität MünchenMunichGermany

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