NK cell-mediated lysis is essential to kill Epstein-Barr virus transformed lymphoblastoid B cells when using rituximab

Laszlo Markasz, Bruno Vanherberghen, Emilie Flaberg, Rita Ötvös, Gyorgy Stuber, Åsa Gustafsson Jernberg, Eva Olah, Henriette Skribek, Laszlo Szekely

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5 Citations (Scopus)

Abstract

Rituximab is a humanized chimeric monoclonal antibody, targeted against the pan B cell marker CD20. It is frequently used to treat a variety of B cell lymphomas and immunosuppression associated lymphoproliferations such as posttransplant lymphoproliferative disorder (PTLD). The response rate of rituximab treatment is 65%, but the exact in vivo mechanism of action is not yet fully understood, although antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and direct induction of apoptosis have been suggested as effector mechanism. Rituximab may affect different types of lymphomas through different mechanisms. As lymphoblastoid cell lines (LCLs) are well-established in vitro models of PTLD, we investigated the effect of rituximab on these cells using a custom built automated laser confocal fluorescent microscope. We found that rituximab alone was not effective at inducing cell death of EBV-transformed B cells. The antibody was effective in the complement-mediated CDC. Rituximab could induce NK cell-mediated ADCC but it was more effective in the presence of untreated fresh human plasma compared to heat-inactivated human plasma. Our data suggest that complement-enhanced NK-mediated ADCC is required for effective rituximab mediated killing of EBV-transformed B cells. Determining and monitoring of serum complement levels and in vitro killing efficacy of NK cells of PTLD patients might help to predict resistant cases to rituximab therapy. On the other hand our results suggest a possibility that rituximab should be combined only with cytotoxic drugs that spare NK function when treating PTLD patients.

Original languageEnglish
Pages (from-to)413-420
Number of pages8
JournalBiomedicine and Pharmacotherapy
Volume63
Issue number6
DOIs
Publication statusPublished - Jul 1 2009

Keywords

  • Complement
  • Killing
  • LCL
  • NK cells
  • PTLD
  • Rituximab

ASJC Scopus subject areas

  • Pharmacology

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    Markasz, L., Vanherberghen, B., Flaberg, E., Ötvös, R., Stuber, G., Gustafsson Jernberg, Å., Olah, E., Skribek, H., & Szekely, L. (2009). NK cell-mediated lysis is essential to kill Epstein-Barr virus transformed lymphoblastoid B cells when using rituximab. Biomedicine and Pharmacotherapy, 63(6), 413-420. https://doi.org/10.1016/j.biopha.2008.08.009