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当前位置: 香港综合肿瘤中心 > PD-1/PD-L1抑制剂资讯 > Pembrolizumab:PD-1的抑制在癌症的治疗策略

Pembrolizumab:PD-1的抑制在癌症的治疗策略

文章出处:未知 责任编辑:admin 作者:admin 发表时间:2016-08-09 09:20

程序性细胞死亡蛋白质1(PD-1)和它的配体,程序性细胞死亡1配体1(PD-L1)和2(PD-L2)的调节通过各种机制的免疫反应中发挥重要作用。此抑制作用被认为通过癌症细胞的PD-1在免疫逃避,以协助和PD-L1和PD-L2已发现由肿瘤微环境中的肿瘤细胞和淋巴细胞异常表达。临床前研究说明导致肿瘤生长抑制PD-1封锁,甚至下降转移。

这样导致pembrolizumab的发展(MK-3475),以高度选择性,人源化单克隆的IgG4-卡帕同种型抗PD-1抗体。

早期的临床试验显示高肿瘤缓解率和在导致加速FDA批准在这种情况下,药物治疗以前的晚期黑色素瘤的效果持续时间长。Pembrolizumab也产生了在非小细胞肺癌的成功,并在多个其他类型的肿瘤被测试。本次审查将讨论开发,临床前数据,药代动力学和临床疗效pembrolizumab日期。

 

Programmed cell death protein 1 (PD-1) and its ligands, programmed cell death 1 ligand 1 (PD-L1) and 2 (PD-L2) play an important role in regulating immune response through various mechanisms. This inhibitory action is thought to assist in immune evasion by cancer cells as PD-1, PD-L1 and PD-L2 have been found to be abnormally expressed by tumor cells and lymphocytes in the tumor microenvironment. Preclinical studies described PD-1 blockade resulting in tumor growth suppression and even decreased metastasis. This has led to the development of pembrolizumab (MK-3475), a highly selective, humanized monoclonal IgG4-kappa isotype antibody against PD-1. Early clinical trials have shown high tumor response rates and long duration of effect in previously treated advanced melanoma resulting in accelerated FDA approval for the drug in this situation. Pembrolizumab has also had success in non-small cell lung cancer and is being tested in multiple other tumor types. This review will discuss the development, preclinical data, pharmacokinetics and clinical efficacy to date of pembrolizumab.

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