Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Cancer Research UK Beatson Institute, Glasgow, UK.
Clin Exp Immunol. 2018 Feb;191(2):133-148. doi: 10.1111/cei.13081. Epub 2017 Dec 27.
Immune checkpoint inhibitors (ICIs) targeting cytotoxic T lymphocyte-associated protein-4 (CTLA-4) or programmed cell death protein 1 (PD-1) receptors have demonstrated remarkable efficacy in subsets of patients with malignant disease. This emerging treatment modality holds great promise for future cancer treatment and has engaged pharmaceutical research interests in tumour immunology. While ICIs can induce rapid and durable responses in some patients, identifying predictive factors for effective clinical responses has proved challenging. This review summarizes the mechanisms of action of ICIs and outlines important preclinical work that contributed to their development. We explore clinical data that has led to disease-specific drug licensing, and highlight key clinical trials that have revealed ICI efficacy across a range of malignancies. We describe how ICIs have been used as part of combination therapies, and explore their future prospects in this area. We conclude by discussing the incorporation of these new immunotherapeutics into precision approaches to cancer therapy.
免疫检查点抑制剂(ICIs)针对细胞毒性 T 淋巴细胞相关蛋白 4(CTLA-4)或程序性细胞死亡蛋白 1(PD-1)受体,在恶性疾病的某些亚组患者中显示出显著的疗效。这种新兴的治疗方式为未来的癌症治疗带来了巨大的希望,并引起了制药界对肿瘤免疫学的兴趣。虽然 ICI 在一些患者中可以诱导快速和持久的反应,但确定有效的临床反应的预测因素一直具有挑战性。这篇综述总结了 ICI 的作用机制,并概述了对其发展有贡献的重要临床前工作。我们探讨了导致特定疾病药物批准的临床数据,并强调了揭示 ICI 疗效的关键临床试验,这些临床试验涉及一系列恶性肿瘤。我们描述了 ICI 如何被用作联合治疗的一部分,并探讨了它们在这一领域的未来前景。最后,我们讨论了将这些新的免疫疗法纳入癌症治疗的精准方法。