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Prepublished online as a Blood First Edition Paper on October 3, 2002; DOI 10.1182/blood-2002-02-0469.
Submitted February 20, 2002
Accepted August 12, 2002
In vitro mechanisms of action of rituximab on primary non-Hodgkin's lymphomas
Olivier Manches, Gabrielle Lui, Laurence Chaperot, Remy Gressin, Jean-Paul Molens, Marie-Christine Jacob, Jean-Jacques Sotto, Dominique Leroux, Jean-Claude Bensa, and Joel Plumas*
Department of Research and Development, Etablissement Francais du Sang, La Tronche, France; Research Group on Lymphoma, Albert Bonniot Institute, La Tronche, France
Clinical Hematological Department, Michallon Hospital, Grenoble, France
Research Group on Lymphoma, Albert Bonniot Institute, La Tronche, France; Clinical Hematological Department, Michallon Hospital, Grenoble, France
Research Group on Lymphoma, Albert Bonniot Institute, La Tronche, France
* Corresponding author; email: joel.plumas{at}wanadoo.fr.
In order to assess the sensitivity of primary non-Hodgkin's lymphoma cells to rituximab-mediated cytotoxicity, we compared the potency of several rituximab-mediated killing mechanisms on fresh lymphoma cells. All lymphoma cells tested were equally sensible to antibody-dependent cell cytotoxicity (ADCC), antibody-mediated phagocytosis of tumor cells, and rituximab-induced apoptosis. However, they were differentially lysed by complement-dependent cytotoxicity (CDC). We found that taking into account both CD20 and complement regulatory protein expression on tumor cells could predict CDC sensitivity in vitro. Importantly, the sensitivity of lymphoma cells to CDC was consistent with the reported different clinical response rates of lymphomas: rituximab induced high CDC killing of FL cells, whereas MCL and DLCL were moderatly sensible to CDC, and SLL were almost all resistant. We propose that CDC is a determinant mechanism of rituximab-induced killing in vivo. Poor sensitivity to CDC in vitro might predict a poor clinical response, whereas high sensitivity to CDC would only indicate a likelihood of response to rituximab treatment.
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