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[免疫偶联物,用于对抗癌症的载药抗体]

[Immunoconjugates, drug-armed antibodies to fight against cancer].

作者信息

Haeuw Jean-François, Caussanel Véronique, Beck Alain

机构信息

Centre d'immunologie Pierre Fabre, 5, avenue Napoléon III, BP 60497, 74160 Saint-Julien-en-Genevois, France. jean.francois.haeuw@ pierre-fabre.com

出版信息

Med Sci (Paris). 2009 Dec;25(12):1046-52. doi: 10.1051/medsci/200925121046.

Abstract

Monoclonal antibodies constitute a growing class of therapeutic agents. They are classically used in combination with chemotherapeutic drugs for cancer treatment. The concept of coupling a cytotoxic agent to an antibody can be viewed as a means to confer a selectivity for tumoral cells to highly cytotoxic drugs which cannot be used in human, or a higher power to antibodies which have a low anti-tumoral activity on their own. Gemtuzumab ozogamicin is the only drug-armed antibody available on the market, for the treatment of acute myeloid leukaemia. Other immunoconjugates are currently under clinical development. The most used cytotoxic agents derive from calicheamicin, maytansin and auristatin, compounds which are 100 to 1 000 fold more toxic than the classical chemotherapeutic drugs. Today, we know that the efficacy of an immunoconjugate depends not only on the coupled cytotoxic agent, but also on the selected target, the coupling method and the linker.

摘要

单克隆抗体构成了一类不断发展的治疗药物。它们传统上与化疗药物联合用于癌症治疗。将细胞毒性剂与抗体偶联的概念可以被视为一种手段,即赋予肿瘤细胞对无法用于人类的高细胞毒性药物的选择性,或者赋予自身抗肿瘤活性较低的抗体更高的效力。吉妥珠单抗奥唑米星是市场上唯一可用的载药抗体,用于治疗急性髓性白血病。其他免疫偶联物目前正处于临床开发阶段。最常用的细胞毒性剂来源于加利车霉素、美登素和澳瑞他汀,这些化合物的毒性比传统化疗药物高100至1000倍。如今,我们知道免疫偶联物的疗效不仅取决于偶联的细胞毒性剂,还取决于所选的靶点、偶联方法和连接子。

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