Enhancement of anti-lymphoma immuno-effects mediated by dendritic cells pulsed with heat-stressed and rituximab-coated CD20+ lymphoma cells.

Rituximab, a CD20-reactive chimeric monoclonal antibody (mAb), induces apoptosis of lymphoma cells and promotes phagocytosis by dendritic cells and produces a cellular immunoresponse by cross-presentation of tumor antigens to T cells. Heat-stressed tumor cells also stimulate dendritic-cell maturation and induce specific cytotoxic T cells against tumor cells by inducing expression of heat-shock proteins. In this study, we used heat-stressed and rituximab-coated CD20+ lymphoma cells as antigens to load onto immature dendritic cells, and found that rituximab-coated CD20+ Raji cells could promote phagocytosis by dendritic cells, and that rituximab-coated or heat-stressed and then rituximab-coated CD20+ Raji cells resulted in increased dendritic cell maturation. Moreover, only CD20+ Raji cells treated with heat and rituximab effectively enhanced the immunostimulating functions of dendritic cells. Thus, our data indicate that rituximab and heat-shock proteins have synergistic effects, resulting in increased induction of cytotoxic T cells against B-cell lymphoma.