正在研发中的程序性死亡受体 1 配体（PD-L1）抑制剂：前景与进展。
PD-L1 inhibitors in the pipeline: Promise and progress.
作者信息
Vanella Vito, Festino Lucia, Strudel Martina, Simeone Ester, Grimaldi Antonio M, Ascierto Paolo A
机构信息
Melanoma, Cancer Immunotherapy and Innovative Therapies Unit - Istituto Nazionale Tumori Fondazione "G. Pascale," Napoli, Italy.
出版信息
Oncoimmunology. 2017 Sep 21;7(1):e1365209. doi: 10.1080/2162402X.2017.1365209. eCollection 2017.
Abstract
Checkpoint inhibitors have improved survival for patients with melanoma, non-small-cell lung cancer (NSCLC), bladder, head and neck and other cancers. Antibodies against PD-L1, including atezolizumab, avelumab and durvalumab, are also being developed and have been approved for various cancers. Compared with anti-CTLA-4 drugs, studies with anti-PD-1/PD-L1 agents have suggested higher response rates and improved survival. Targeting PD-L1 rather than PD-1 may also theoretically offer further benefit, with the potential for improved efficacy and reduced toxicity, although this has not been clearly shown by clinical experience to date. Anti-PD-L1 agents have shown good efficacy and manageable toxicity in several tumor types.
摘要
检查点抑制剂已提高了黑色素瘤、非小细胞肺癌（NSCLC）、膀胱癌、头颈癌和其他癌症患者的生存率。针对程序性死亡受体配体1（PD-L1）的抗体，包括阿替利珠单抗、阿维鲁单抗和度伐鲁单抗，也正在研发中，并且已被批准用于多种癌症。与抗细胞毒性T淋巴细胞相关蛋白4（CTLA-4）药物相比，抗程序性死亡蛋白1（PD-1）/PD-L1药物的研究表明其具有更高的缓解率和更长的生存期。理论上，靶向PD-L1而非PD-1可能会带来更多益处，有可能提高疗效并降低毒性，尽管迄今为止临床经验尚未明确证实这一点。抗PD-L1药物在多种肿瘤类型中已显示出良好的疗效和可管理的毒性。
相似文献
1
PD-L1 inhibitors in the pipeline: Promise and progress.正在研发中的程序性死亡受体 1 配体（PD-L1）抑制剂：前景与进展。
Oncoimmunology. 2017 Sep 21;7(1):e1365209. doi: 10.1080/2162402X.2017.1365209. eCollection 2017.
2
Immune Checkpoint Inhibitors and Cardiac Toxicity: An Emerging Issue.免疫检查点抑制剂与心脏毒性：一个新出现的问题。
Curr Med Chem. 2018;25(11):1327-1339. doi: 10.2174/0929867324666170407125017.
3
The Evolving Role of PD-L1 Inhibition in Non-Small Cell Lung Cancer: A Review of Durvalumab and Avelumab.程序性死亡受体 1 配体（PD-L1）抑制在非小细胞肺癌中的角色演变：度伐鲁单抗和阿维鲁单抗综述
Cancer Med J. 2022 Apr;5(1):31-45. Epub 2021 Dec 7.
4
New insight in endocrine-related adverse events associated to immune checkpoint blockade.免疫检查点阻断相关内分泌不良事件的新认识。
Best Pract Res Clin Endocrinol Metab. 2020 Jan;34(1):101370. doi: 10.1016/j.beem.2019.101370. Epub 2019 Dec 11.
5
Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment-A Review From the Melanoma Perspective and Beyond.免疫检查点抑制剂治疗临床获益的生物标志物——从黑色素瘤及其他角度的综述
Front Immunol. 2018 Jun 28;9:1474. doi: 10.3389/fimmu.2018.01474. eCollection 2018.
6
The Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma.下一代免疫检查点抑制剂：黑色素瘤中的PD-1/PD-L1阻断
Clin Ther. 2015 Apr 1;37(4):764-82. doi: 10.1016/j.clinthera.2015.02.018. Epub 2015 Mar 29.
7
Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study.度伐利尤单抗作为晚期非小细胞肺癌的三线或后线治疗药物（ATLANTIC）：一项开放标签、单臂、2 期研究。
Lancet Oncol. 2018 Apr;19(4):521-536. doi: 10.1016/S1470-2045(18)30144-X. Epub 2018 Mar 12.
8
Advanced non-small cell lung cancer: the role of PD-L1 inhibitors.晚期非小细胞肺癌：PD-L1抑制剂的作用
J Thorac Dis. 2018 May;10(Suppl 13):S1468-S1473. doi: 10.21037/jtd.2018.01.112.
9
Targeting the PD-1/PD-L1 axis in non-small cell lung cancer.靶向非小细胞肺癌中的PD-1/PD-L1轴
Curr Probl Cancer. 2017 Mar-Apr;41(2):111-124. doi: 10.1016/j.currproblcancer.2016.12.002. Epub 2016 Dec 23.
10
The relationship between blood-based tumor mutation burden level and efficacy of PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis.基于血液的肿瘤突变负担水平与 PD-1/PD-L1 抑制剂在晚期非小细胞肺癌中的疗效关系：系统评价和荟萃分析。
BMC Cancer. 2021 Nov 13;21(1):1220. doi: 10.1186/s12885-021-08924-z.
引用本文的文献
1
Targeting PD-L1 in cholangiocarcinoma using nanovesicle-based immunotherapy.使用基于纳米囊泡的免疫疗法靶向胆管癌中的程序性死亡受体配体1（PD-L1）
Mol Ther. 2024 Aug 7;32(8):2762-2777. doi: 10.1016/j.ymthe.2024.06.006. Epub 2024 Jun 10.
2
Effect of Fragment 1 on the Binding of Epigallocatechin Gallate to the PD-L1 Dimer Explored by Molecular Dynamics.分子动力学探究 Fragment 1 对 EGCG 与 PD-L1 二聚体结合的影响。
Molecules. 2023 Nov 30;28(23):7881. doi: 10.3390/molecules28237881.
3
Local immune checkpoint blockade therapy by an adenovirus encoding a novel PD-L1 inhibitory peptide inhibits the growth of colon carcinoma in immunocompetent mice.通过编码新型PD-L1抑制肽的腺病毒进行局部免疫检查点阻断疗法可抑制免疫健全小鼠体内结肠癌的生长。
Transl Oncol. 2022 Feb;16:101337. doi: 10.1016/j.tranon.2021.101337. Epub 2022 Jan 3.
4
EV PD-L1 Contributes to Immunosuppressive CD8 T Cells in Peripheral Blood of Pediatric Wilms Tumor.EV PD-L1 有助于小儿肾母细胞瘤外周血中免疫抑制性 CD8 T 细胞。
Technol Cancer Res Treat. 2021 Jan-Dec;20:15330338211041264. doi: 10.1177/15330338211041264.
5
The Value of Hope: Patients' and Physicians' Preferences for Survival in Advanced Non-Small Cell Lung Cancer.希望的价值：晚期非小细胞肺癌患者及医生对生存的偏好
Patient Prefer Adherence. 2020 Oct 30;14:2093-2104. doi: 10.2147/PPA.S248295. eCollection 2020.
6
The Association Between Immune Characteristic and Clinical Pathology in Chinese Patients with Adenocarcinoma of Esophagogastric Junction.中国食管胃交界腺癌患者免疫特征与临床病理的相关性
Cancer Manag Res. 2020 May 11;12:3259-3269. doi: 10.2147/CMAR.S235722. eCollection 2020.
7
Phase I Study of the Bifunctional Fusion Protein Bintrafusp Alfa in Asian Patients with Advanced Solid Tumors, Including a Hepatocellular Carcinoma Safety-Assessment Cohort.Bintrafusp Alfa 双功能融合蛋白在亚洲晚期实体瘤患者中的 I 期研究，包括一个肝细胞癌安全性评估队列。
Oncologist. 2020 Sep;25(9):e1292-e1302. doi: 10.1634/theoncologist.2020-0249. Epub 2020 Apr 23.
8
Comprehensive in vitro characterization of PD-L1 small molecule inhibitors.全面的 PD-L1 小分子抑制剂的体外表征。
Sci Rep. 2019 Aug 27;9(1):12392. doi: 10.1038/s41598-019-48826-6.
9
Monitoring Patient Response to Pembrolizumab With Peripheral Blood Exhaustion Marker Profiles.通过外周血耗竭标志物谱监测患者对帕博利珠单抗的反应。
Front Med (Lausanne). 2019 May 22;6:113. doi: 10.3389/fmed.2019.00113. eCollection 2019.
10
Modelling of Protein Kinase Signaling Pathways in Melanoma and Other Cancers.黑色素瘤及其他癌症中蛋白激酶信号通路的建模
Cancers (Basel). 2019 Apr 3;11(4):465. doi: 10.3390/cancers11040465.
本文引用的文献
1
Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial.阿维鲁单抗治疗铂类治疗失败后的转移性尿路上皮癌（JAVELIN Solid Tumor）：一项开放标签、1 期试验两个扩展队列的汇总结果。
Lancet Oncol. 2018 Jan;19(1):51-64. doi: 10.1016/S1470-2045(17)30900-2. Epub 2017 Dec 5.
2
Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study.阿维鲁单抗，一种抗程序性死亡配体1抗体，用于难治性转移性尿路上皮癌患者：一项多中心1b期研究的结果
J Clin Oncol. 2017 Jul 1;35(19):2117-2124. doi: 10.1200/JCO.2016.71.6795. Epub 2017 Apr 4.
3
Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial.阿维鲁单抗用于既往接受过治疗的转移性或复发性非小细胞肺癌患者（JAVELIN实体瘤研究）：一项多中心、开放标签的1b期试验的剂量扩展队列研究
Lancet Oncol. 2017 May;18(5):599-610. doi: 10.1016/S1470-2045(17)30240-1. Epub 2017 Mar 31.
4
Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial.伊匹单抗 10mg/kg 对比伊匹单抗 3mg/kg 治疗不可切除或转移性黑色素瘤患者：一项随机、双盲、多中心、III 期临床试验。
Lancet Oncol. 2017 May;18(5):611-622. doi: 10.1016/S1470-2045(17)30231-0. Epub 2017 Mar 27.
5
Immune-related response assessment during PD-1 inhibitor therapy in advanced non-small-cell lung cancer patients.晚期非小细胞肺癌患者接受PD-1抑制剂治疗期间的免疫相关反应评估
J Immunother Cancer. 2016 Dec 20;4:84. doi: 10.1186/s40425-016-0193-2. eCollection 2016.
6
Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial.阿替利珠单抗用于铂类不适用的局部晚期和转移性尿路上皮癌患者的一线治疗：一项单臂、多中心、2期试验。
Lancet. 2017 Jan 7;389(10064):67-76. doi: 10.1016/S0140-6736(16)32455-2. Epub 2016 Dec 8.
7
Immunoscore and Immunoprofiling in cancer: an update from the melanoma and immunotherapy bridge 2015.癌症中的免疫评分与免疫剖析：来自2015年黑色素瘤与免疫治疗桥梁会议的最新进展
J Transl Med. 2016 Sep 20;14:273. doi: 10.1186/s12967-016-1029-z.
8
Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial.阿维鲁单抗治疗化疗难治性转移性默克尔细胞癌患者：一项多中心、单组、开放标签的2期试验。
Lancet Oncol. 2016 Oct;17(10):1374-1385. doi: 10.1016/S1470-2045(16)30364-3. Epub 2016 Sep 1.
9
Malignant Mesothelioma Effusions Are Infiltrated by CD3 T Cells Highly Expressing PD-L1 and the PD-L1 Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab.恶性间皮瘤积液被高表达PD-L1的CD3 T细胞浸润，且这些积液中的PD-L1肿瘤细胞对抗PD-L1抗体阿维鲁单抗介导的ADCC敏感。
J Thorac Oncol. 2016 Nov;11(11):1993-2005. doi: 10.1016/j.jtho.2016.07.033. Epub 2016 Aug 17.
10
Programmed Death-1 Ligand 2-Mediated Regulation of the PD-L1 to PD-1 Axis Is Essential for Establishing CD4(+) T Cell Immunity.程序性死亡受体-1 配体 2 调节 PD-L1 与 PD-1 轴对于建立 CD4(+) T 细胞免疫至关重要。
Immunity. 2016 Aug 16;45(2):333-45. doi: 10.1016/j.immuni.2016.07.017.
Zotero 插件