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程序性死亡蛋白1及其配体:癌症免疫治疗的潜在靶点。

Programmed death-1 & its ligands: promising targets for cancer immunotherapy.

作者信息

Shrimali Rajeev K, Janik John E, Abu-Eid Rasha, Mkrtichyan Mikayel, Khleif Samir N

机构信息

Georgia Regents University Cancer Center, Augusta, GA 30912, USA.

出版信息

Immunotherapy. 2015;7(7):777-92. doi: 10.2217/imt.15.49. Epub 2015 Aug 7.

Abstract

Novel strategies for cancer treatment involving blockade of immune inhibitors have shown significant progress toward understanding the molecular mechanism of tumor immune evasion. The preclinical findings and clinical responses associated with programmed death-1 (PD-1) and PD-ligand pathway blockade seem promising, making these targets highly sought for cancer immunotherapy. In fact, the anti-PD-1 antibodies, pembrolizumab and nivolumab, were recently approved by the US FDA for the treatment of unresectable and metastatic melanoma resistant to anticytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) and BRAF inhibitor. Here, we discuss strategies of combining PD-1/PD-ligand interaction inhibitors with other immune checkpoint modulators and standard-of-care therapy to break immune tolerance and induce a potent antitumor activity, which is currently a research area of key scientific pursuit.

摘要

涉及阻断免疫抑制剂的癌症治疗新策略在理解肿瘤免疫逃逸的分子机制方面已取得显著进展。与程序性死亡-1(PD-1)和PD-配体途径阻断相关的临床前研究结果和临床反应似乎很有前景,这使得这些靶点成为癌症免疫治疗中备受追捧的对象。事实上,抗PD-1抗体帕博利珠单抗和纳武利尤单抗最近已被美国食品药品监督管理局批准用于治疗对抗细胞毒性T淋巴细胞抗原-4抗体(伊匹木单抗)和BRAF抑制剂耐药的不可切除和转移性黑色素瘤。在此,我们讨论将PD-1/PD-配体相互作用抑制剂与其他免疫检查点调节剂及标准治疗方法相结合以打破免疫耐受并诱导强大抗肿瘤活性的策略,这是目前关键科学探索的研究领域。

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