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[肿瘤血液学中的治疗性单克隆抗体]

[Therapeutic monoclonal antibodies in onco-hematology].

作者信息

Cartron Guillaume, Rossi Jean-François

机构信息

Service d'hématologie et biothérapies, Centre d'investigation clinique biothérapies, CHU de Montpellier, 191, avenue du doyen Gaston Giraud, 34295 Montpellier, France.

出版信息

Med Sci (Paris). 2009 Dec;25(12):1085-9. doi: 10.1051/medsci/200925121085.

Abstract

Rituximab, a chimeric monoclonal anti-CD20 antibody, was introduced into clinical practice in 1997, and has proven to be highly effective in the treatment of B-lymphoproliferative disorders and autoimmune diseases. Despite such success, in vivo mechanisms of action of anti-CD20 have only recently began to be unraveled, pointing to the crucial role of antibody-dependent cellular cytotoxicity response mediated through Fcg receptor signalling. Better understanding of pharmacokinetics and factors influencing individual exposure mediated through anti-CD20 will allow to engineer these molecules to increase their effector responses. Meanwhile, other formats have also been investigated, such as radiolabeled anti-CD20, or coupling of antibodies to cytotoxic drugs such as anti-CD33 used in myeloid leukemia. However these antibodies are used in combination with standard chemotherapy and cannot substitute for cytotoxic drugs. This review summarizes the knowledge acquired through our clinical use of anti-CD20 and authorized monoclonal antibodies in oncohematology and proposes some news areas that will lead to the development of new and more effective therapeutic strategies.

摘要

利妥昔单抗是一种嵌合单克隆抗CD20抗体,于1997年引入临床实践,已被证明在治疗B淋巴细胞增殖性疾病和自身免疫性疾病方面非常有效。尽管取得了这样的成功,但抗CD20的体内作用机制直到最近才开始被揭示,这表明通过Fcg受体信号介导的抗体依赖性细胞毒性反应起着关键作用。更好地了解抗CD20介导的药代动力学和影响个体暴露的因素,将有助于设计这些分子以增强其效应反应。同时,也研究了其他形式,如放射性标记的抗CD20,或将抗体与细胞毒性药物偶联,如用于髓系白血病的抗CD33。然而,这些抗体与标准化疗联合使用,不能替代细胞毒性药物。本综述总结了我们在肿瘤血液学中临床使用抗CD20和已获批单克隆抗体所获得的知识,并提出了一些新的领域,这些领域将引领新的、更有效的治疗策略的发展。

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