药学学报, 2012, 47(10): 1306-1316
引用本文:
孙 巍, 林 珩, 花 芳, 胡卓伟. 治疗性抗体: 炎性免疫性疾病治疗的新选择[J]. 药学学报, 2012, 47(10): 1306-1316.
SUN Wei, LIN Heng, HUA Fang, HU Zhuo-wei. Therapeutic antibody: new opportunity for immunity and inflammatory diseases[J]. Acta Pharmaceutica Sinica, 2012, 47(10): 1306-1316.

治疗性抗体: 炎性免疫性疾病治疗的新选择
孙  巍, 林  珩, 花  芳, 胡卓伟*
(中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050)
摘要:

治疗性抗体经历数十年的发展已经成为治疗人类疾病包括炎性免疫性疾病的主要药物。利用人源化或全人化技术制备单克隆抗体, 降低了鼠源抗体在人体中的免疫原性, 提高了抗体的生物活性及半衰期, 并成功获得多种治疗性抗体。目前, 使用治疗性抗体治疗的炎性免疫性疾病包括移植排斥、自身免疫病、自身炎症病及过敏性疾病。预期与炎症免疫相关的治疗性抗体将会有广阔的应用前景。治疗性抗体通过阻断配体或受体、调控受体、清除靶细胞或激活受体等机制发挥靶向治疗作用。通过基因工程手段改造抗体的Fc段来优化抗体的生物学功能, 以及改造与抗原结合的结构域, 能够生成新的疗效更高、副作用更少的抗体药物。

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Therapeutic antibody: new opportunity for immunity and inflammatory diseases
Abstract:

With the development of therapeutic antibodies over the past decade, they have become the treatment options for immunity and inflammation diseases.  Major limitations of mouse antibodies as therapeutic agents — immunogenicity, lack of effectors’ functions and short serum half-life — were subsequently identified and largely overcome by the advent of humanized and fully human antibody technologies.  The therapeutic antibodies for immunity and inflammatory diseases are primarily utilized in the treatment of allograft rejection, autoimmune disease, autoinflammatory syndromes, allergies and other chronic inflammation.  The action mechanisms of therapeutic antibody include blocking ligands or receptors, regulating receptor activity, clearing the target cells or activating receptor.  Strategies for generating the antibody drugs with high efficacy and low side effects can be realized by modulation of Fc-mediated activities and optimization of antigen-binding domains.

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