文章：

用抗体治疗癌症

Cancer therapy with antibodies

原文发布日期：2024-05-13

DOI: 10.1038/s41568-024-00690-x

类型: Review Article

开放获取: 否

英文摘要：

The greatest challenge in cancer therapy is to eradicate cancer cells with minimal damage to normal cells. Targeted therapy has been developed to meet that challenge, showing a substantially increased therapeutic index compared with conventional cancer therapies. Antibodies are important members of the family of targeted therapeutic agents because of their extraordinarily high specificity to the target antigens. Therapeutic antibodies use a range of mechanisms that directly or indirectly kill the cancer cells. Early antibodies were developed to directly antagonize targets on cancer cells. This was followed by advancements in linker technologies that allowed the production of antibody–drug conjugates (ADCs) that guide cytotoxic payloads to the cancer cells. Improvement in our understanding of the biology of T cells led to the production of immune checkpoint-inhibiting antibodies that indirectly kill the cancer cells through activation of the T cells. Even more recently, bispecific antibodies were synthetically designed to redirect the T cells of a patient to kill the cancer cells. In this Review, we summarize the different approaches used by therapeutic antibodies to target cancer cells. We discuss their mechanisms of action, the structural basis for target specificity, clinical applications and the ongoing research to improve efficacy and reduce toxicity.

摘要翻译： 

癌症治疗面临的最大挑战是在尽可能减少对正常细胞损害的前提下根除癌细胞。靶向疗法的开发正是为了应对这一挑战，与传统癌症疗法相比，其治疗指数显著提高。抗体因其对靶抗原具有极高特异性，成为靶向治疗药物家族中的重要成员。治疗性抗体通过直接或间接杀伤癌细胞的多种机制发挥作用：早期开发的抗体直接作用于癌细胞靶点；随着连接技术的进步，抗体药物偶联物（ADCs）得以引导细胞毒性有效载荷靶向癌细胞；对T细胞生物学的深入理解催生了免疫检查点抑制性抗体，通过激活T细胞间接杀伤癌细胞；最新开发的双特异性抗体则能重定向患者自身的T细胞来消灭癌细胞。本文综述了治疗性抗体靶向癌细胞的不同策略，探讨其作用机制、靶向特异性的结构基础、临床应用现状，以及当前在提升疗效和降低毒性方面的研究进展。

原文链接：

Cancer therapy with antibodies