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.

癌症治疗的最大挑战是在对正常细胞的损害最小的情况下根除癌细胞。靶向疗法已经开发出来应对这一挑战，与传统癌症疗法相比，治疗指数显着提高。抗体是靶向治疗剂家族的重要成员，因为它们对靶抗原具有极高的特异性。治疗性抗体使用一系列直接或间接杀死癌细胞的机制。早期抗体被开发用于直接拮抗癌细胞上的靶标。随后是接头技术的进步，允许产生抗体-药物偶联物 （ADC），将细胞毒性有效载荷引导至癌细胞。我们对 T 细胞生物学的理解的提高导致了免疫检查点抑制抗体的产生，这些抗体通过激活 T 细胞间接杀死癌细胞。甚至最近，双特异性抗体被合成设计来重定向患者的 T 细胞以杀死癌细胞。在这篇综述中，我们总结了治疗性抗体用于靶向癌细胞的不同方法。我们讨论了它们的作用机制、靶点特异性的结构基础、临床应用以及正在进行的提高疗效和降低毒性的研究。