Oncology R&D, GlaxoSmithKline, Collegeville, PA, USA.
Incyte, Wilmington, DE, USA.
Nat Rev Drug Discov. 2018 Jul;17(7):509-527. doi: 10.1038/nrd.2018.75. Epub 2018 Jun 15.
Immune cell functions are regulated by co-inhibitory and co-stimulatory receptors. The first two generations of cancer immunotherapy agents consist primarily of antagonist antibodies that block negative immune checkpoints, such as programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte protein 4 (CTLA4). Looking ahead, there is substantial promise in targeting co-stimulatory receptors with agonist antibodies, and a growing number of these agents are making their way through various stages of development. This Review discusses the key considerations and potential pitfalls of immune agonist antibody design and development, their differentiating features from antagonist antibodies and the landscape of agonist antibodies in clinical development for cancer treatment.
免疫细胞的功能受共抑制和共刺激受体的调节。第一代和第二代癌症免疫治疗药物主要由拮抗抗体组成，这些抗体可以阻断负性免疫检查点，如程序性细胞死亡蛋白 1（PD1）和细胞毒性 T 淋巴细胞相关抗原 4（CTLA4）。展望未来，用激动剂抗体靶向共刺激受体具有很大的前景，越来越多的这类药物正在通过不同的开发阶段。这篇综述讨论了免疫激动剂抗体设计和开发的关键考虑因素和潜在陷阱，以及它们与拮抗剂抗体的区别特征和在癌症治疗中临床开发的激动剂抗体的现状。
