Golay Joseè, Gramigna Rosanna, Facchinetti Valeria, Capello Daniela, Gaidano Gianluca, Introna Martino
Laboratory of Molecular Immunohaematology, Department of Immunology and Cell Biology, Istituto Ricerche Farmacologiche Mario Negri, Milan, Italy.
Br J Haematol. 2002 Dec;119(4):923-9. doi: 10.1046/j.1365-2141.2002.03935.x.
Rituximab (Mabthera) and alemtuzumab (Campath(R), Mabcampath(R)) are non-conjugated IgG1 therapeutic monoclonal antibodies directed against the CD20 and CD52 surface antigens respectively. They are presently used in the therapy of indolent B-cell non-Hodgkin's lymphoma (B-NHL) and of B-cell chronic lymphocytic leukaemia, and are thought to act mainly through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Here we have analysed the capacity of these two monoclonal antibodies to lyse cell lines of acquired immunodeficiency syndrome (AIDS)-related B-NHL through either complement activation or antibody-dependent cytotoxicity. Rituximab strongly activated both CDC and ADCC against CD20-positive AIDS-NHL cells lines, inducing up to 60-98% and 20% specific lysis respectively. In contrast, alemtuzumab was a poor activator of CDC, even in the AIDS-NHL cell lines expressing high amounts of CD52, leading to a lysis of only 1-30%, whereas it was at least as strong as rituximab in inducing ADCC of the same lines (up to 30% specific lysis). Altogether, these data offer a first in vitro rationale supporting the therapeutic use of rituximab for CD20-positive AIDS-NHL.
利妥昔单抗（美罗华）和阿仑单抗（坎帕替，Mabcampath）分别是针对CD20和CD52表面抗原的非共轭IgG1治疗性单克隆抗体。它们目前用于惰性B细胞非霍奇金淋巴瘤（B-NHL）和B细胞慢性淋巴细胞白血病的治疗，并且被认为主要通过补体依赖性细胞毒性（CDC）和抗体依赖性细胞毒性（ADCC）发挥作用。在此，我们分析了这两种单克隆抗体通过补体激活或抗体依赖性细胞毒性作用裂解获得性免疫缺陷综合征（AIDS）相关B-NHL细胞系的能力。利妥昔单抗强烈激活针对CD20阳性AIDS-NHL细胞系的CDC和ADCC，分别诱导高达60%-98%和20%的特异性裂解。相比之下，阿仑单抗即使在表达大量CD52的AIDS-NHL细胞系中也是较差的CDC激活剂，导致仅1%-30%的细胞裂解，而在诱导同系细胞的ADCC方面，它至少与利妥昔单抗一样强（高达30%的特异性裂解）。总之，这些数据首次提供了体外理论依据，支持利妥昔单抗用于CD20阳性AIDS-NHL的治疗。
