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作者：SCI天天读
SCI
26 May 2024
Cancer therapy with antibodies
(Nature Reviews Cancer, IF: 78.5)
Suman Paul, Maximilian F. Konig, Drew M. Pardoll, Chetan Bettegowda, Nickolas Papadopoulos, Katharine M. Wright, Sandra B. Gabelli, Mitchell Ho, Andrea van Elsas, & Shibin Zhou
CORRESPONDENCE TO: spaul19@jhmi.edu; sandra.gabelli@merck.com; homi@mail.nih.gov;avanelsas@thirdrockventures.com
Abstract 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.
癌症治疗的最大挑战是在对正常细胞损伤最小的情况下根除癌症细胞。靶向治疗特以应对这一挑战，其与传统癌症治疗相比，治疗指数显著提高。抗体是靶向治疗家族的重要成员，因为它们对靶抗原具有极高的特异性。治疗性抗体有一系列直接或间接杀死癌症细胞的机制。早期抗体被开发用于直接拮抗癌症细胞上的靶点。随后，连接子技术的进步使得抗体-药物偶联物（ADC）的生产得以进行，从而将细胞毒性有效载荷引导至癌症细胞。我们对T细胞生物学理解的提高导致了免疫检查点抑制抗体的产生，该抗体通过激活T细胞间接杀死癌症细胞。甚至在最近，合成设计的双特异性抗体可重定向患者的T细胞以杀死癌症细胞。在这篇综述中，我们总结了治疗性抗体靶向癌症细胞的不同方法。我们讨论了它们的作用机制、靶点特异性的结构基础、临床应用以及正在开展的可提高疗效和降低毒性的研究。
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