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[抗体疗法:从实验室到临床应用]

[Antibody Therapeutics: Bench to Bedside].

作者信息

Sakanaka Chie

机构信息

Pharmaceuticals and Medical Devices Agency (PMDA).

出版信息

Yakugaku Zasshi. 2017;137(7):817-822. doi: 10.1248/yakushi.16-00252-1.

Abstract

Monoclonal antibodies have been considered promising therapeutic entities due to their highly specific binding to antigens. For oncology in particular, the tumor specific binding of an antibody, without affecting normal tissue, is considered an ideal cancer therapy. Although the proposed mechanism of action of antibody therapeutics varies by targets and indications, antibody-dependent cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), ligand neutralization and inhibition of the signaling pathway are commonly used. Recent advances in genomic information, genetic engineering, and transgenic technology have greatly accelerated drug development processes. It is also possible to add new functions to antibody molecules through molecular engineering. For example, antibody-drug conjugates (ADC), which combine a monoclonal antibody and a small-molecule cytotoxic drug, have been successfully used for cancer treatment. It has been more than 20 years since the first therapeutic antibody was approved in Japan, and there are now more than 30 antibodies on the market, with many new molecules under development. Despite some drawbacks and challenges, antibody therapeutics hold great promise as we advance our knowledge and technologies in the coming years.

摘要

单克隆抗体因其与抗原的高度特异性结合而被视为有前景的治疗实体。特别是对于肿瘤学而言,抗体与肿瘤特异性结合且不影响正常组织,被认为是理想的癌症治疗方法。尽管抗体疗法的作用机制因靶点和适应症而异,但抗体依赖性细胞毒性(ADCC)、补体依赖性细胞毒性(CDC)、配体中和以及信号通路抑制是常用的机制。基因组信息、基因工程和转基因技术的最新进展极大地加速了药物开发进程。通过分子工程向抗体分子添加新功能也是可能的。例如,将单克隆抗体与小分子细胞毒性药物相结合的抗体药物偶联物(ADC)已成功用于癌症治疗。自第一种治疗性抗体在日本获批以来已有20多年,目前市场上有30多种抗体,还有许多新分子正在研发中。尽管存在一些缺点和挑战,但随着我们在未来几年不断推进知识和技术,抗体疗法仍具有巨大的潜力。

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