Selenko N, Maidic O, Draxier S, Berer A, Jäger U, Knapp W, Stöckl J
Institute of Immunology and Department of Internal Medicine-I, University of Vienna Medical School, Austria.
Leukemia. 2001 Oct;15(10):1619-26. doi: 10.1038/sj.leu.2402226.
C2B8 (Rituximab, MabThera) is a chimeric mouse/human monoclonal antibody (mAb) 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-Hodgkin lymphomas (NHL). Treatment of CD20+ B cells with C2B8 triggers different 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 called cross-presentation. In this study, we investigated whether C2B8 treatment of lymphoma promotes the induction of CD8+ T cell responses against lymphoma cell-associated antigens via, cross-presentation. We used Daudi lymphoma cells as a model system in our studies and could demonstrate, that C2B8-treated Daudi cells undergo apoptosis, are phagocytosed by DC and induce in DC typical features of maturation; among them, the induction of CD83 expression as well as the up-regulation of prominent accessory molecules (CD40, CD86) and MHC molecules. Importantly, upon co-culture of such lymphoma cell-pulsed DC with autologous T cells, we could induce efficient cytotoxic T cell (CTL) responses against Daudi cell-associated antigens. These findings suggest that antibody treatment of tumor cells can, in addition to its direct cell damaging effects, under certain conditions, contribute to an induction of potentially protective cytotoxic T cell responses.
C2B8（利妥昔单抗，美罗华）是一种嵌合型鼠/人单克隆抗体（mAb），它靶向人类B细胞限制性细胞表面抗原CD20，被用作治疗B细胞非霍奇金淋巴瘤（NHL）的替代药物。用C2B8处理CD20+B细胞会引发不同的细胞损伤效应，包括肿瘤细胞的补体依赖性裂解、抗体依赖性细胞毒性和凋亡诱导。树突状细胞（DC）最近被证明能够摄取细胞碎片并呈递相关抗原，甚至在MHC I类分子上呈递，这一机制称为交叉呈递。在本研究中，我们调查了用C2B8治疗淋巴瘤是否通过交叉呈递促进针对淋巴瘤细胞相关抗原的CD8+T细胞反应的诱导。我们在研究中使用Daudi淋巴瘤细胞作为模型系统，并能够证明，经C2B8处理的Daudi细胞会发生凋亡，被DC吞噬，并在DC中诱导成熟的典型特征；其中包括CD83表达的诱导以及显著辅助分子（CD40、CD86）和MHC分子的上调。重要的是，当这种淋巴瘤细胞脉冲的DC与自体T细胞共培养时，我们能够诱导针对Daudi细胞相关抗原的高效细胞毒性T细胞（CTL）反应。这些发现表明，肿瘤细胞的抗体治疗除了具有直接的细胞损伤作用外，在某些情况下还可能有助于诱导潜在的保护性细胞毒性T细胞反应。
