CD20 antibody (C2B8)-induced apoptosis of lymphoma cells promotes phagocytosis by dendritic cells and cross-priming of CD8(+) cytotoxic T cells

C2B8 (Rituximab, MabThera) is a chimeric mouse/human monoclonal antibody (m Ab) directed against the human B cell-restricted cell surface antigen CD20 which is used as an alternative medication in the treatment of B cell non-H odgkin lymphomas (NHL). Treatment of CD20(+) B cells with C2B8 triggers dif ferent cell damaging effects including complement-dependent lysis of tumor cells, antibody-dependent cellular cytotoxicity and induction of apoptosis. Dendritic cells (DC) have recently been shown to ingest cell debris and to present associated antigens even on MHC class I molecules, a mechanism cal led cross-presentation. In this study, we investigated whether C2B8 treatme nt of lymphoma promotes the induction of CD8(+) T cell responses against ly mphoma cell-associated antigens via, cross-presentation. We used Daudi lymp homa cells as a model system in our studies and could demonstrate, that C2B 8-treated Daudi cells undergo apoptosis, are phagocytosed by DC and induce in DC typical features of maturation; among them, the induction of CD83 exp ression as well as the up-regulation of prominent accessory molecules (CD40 , CD86) and MHC molecules. Importantly, upon co-culture of such lymphoma ce ll-pulsed DC with autologous T cells, we could induce efficient cytotoxic T cell (CTL) responses against Daudi cell-associated antigens. These finding s suggest that antibody treatment of tumor cells can, in addition to its di rect cell damaging effects, under certain conditions, contribute to an indu ction of potentially protective cytotoxic T cell responses.