抗CD20单克隆抗体治疗B 细胞淋巴瘤的效应机制

B细胞淋巴瘤是一种主要的非霍奇金淋巴瘤(non-Hodgkin’s lymphoma,NHL),95%以上的B细胞淋巴瘤均表达B细胞分化抗原CD20。尽管目前CD20在B细胞分化发育过程中的具体功能尚未阐明,但其特有的表达方式和在细胞膜上的分布特点决定了其成为B细胞淋巴瘤靶向治疗的主要靶点。近十年来,随着抗CD20单克隆抗体的不断发展和进步,联合传统的CHOP化疗方案,在NHL的治疗中显示出良好的效果。虽然,近年来抗CD20单抗逐渐被用于B细胞相关的自身免疫病的治疗,但相关作用机制尚不明确。在针对NHL的临床治疗中,抗CD20单抗的疗效被认为依赖于效应器机制,主要有ADCC、CDC和细胞凋亡。虽然抗CD20在淋巴瘤的治疗中具有显著的免疫疗效,但部分瘤荷较大的病人出现了耐药和复发,循环中大量B细胞由于单抗的结合而被机体的单核巨噬细胞吞噬或NK细胞杀伤,机体出现成熟B细胞空缺期,同时单核巨噬细胞、NK细胞和补体大量消耗,造成机体免疫效应功能饱和和效应器耗竭。本文就抗CD20单克隆抗体在治疗淋巴瘤中的具体作用机制及可能造成的机体效应器耗竭问题做一简要的概述。

Effector Mechanisms of Anti-CD20 Monoclonal Antibodies in Killing B-cell Lymphoma

B-cell lymphoma is one major kind of non-Hodgkin''s lymphoma (NHL), and more than 95 percent of B-cell lymphomas have B-cell differentiation antigen-CD20 expressed on cellular surface. Although the function of CD20 in B-cell development is not clear, its expression pattern and distribution feature in cytoplasmic membrane have made CD20 the primary therapeutic target in B-cell lymphoma. During recent years, combined with CHOP chemotherapy, some of new-type anti-CD20 monoclonal antibodies have emerged and showed great therapeutic effects on NHLs. Although there have been several reports about successful treatments on autoimmune diseases by anti-CD20 monoclonal antibodies, the specific mechanismhas not been clarified. The effector mechanism is considered to be responsible for therapeutic effect of anti-CD20 monoclonal antibodies on NHL, which includes ADCC, CDC and apoptosis. Though anti-CD20 monoclonal antibodies have showed substantial therapeutic efficacy on NHL, for some patients of high tumor burden drug resistance or relapse occurs after therapy. For these patients, a very significant depletion of B-cell subpopulations appears in the peripheral blood due to phagocytosis by monocyte-macrophages or cytotoxicity by NK cells, and there is a remarkable exhaustion of NK cells, complements and monocyte-macrophages of the body''s immune system. The effector function of their bodies saturates and exhausts. This review illustrated the effector mechanism and the problem of effector exhaustion of anti-CD20 monoclonal antibodies in treating B-cell lymphomas. B