Pento Joseph Thomas
Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma, Health Sciences Center, Oklahoma, OK, U.S.A.
Anticancer Res. 2017 Nov;37(11):5935-5939. doi: 10.21873/anticanres.12040.
The ability of cancer cells to evade the immune system is one of the most deadly characteristics of the majority of malignant tumours. Accordingly, the recent development of antibodies which target tumor cell evasion of immune checkpoints such as the cytotoxic T lymphocyte associated antigen-4 (CTLA-4) as well as the programmed cell death protein (PD-1) and the PD-1 ligand (PD-L1) has been a major and apparently highly effective approach in the treatment and/or eradication of a variety of highly malignant forms of cancers. The US Food and Drug Administration (FDA) has recently approved the application of lpilimumab (which targets CTLA-4) and pembrolizumab (targeting PD-1) for the treatment of advanced gastric cancer. Indeed, various checkpoint blockade antibodies have been approved or have been under clinical investigation. An indication of the renewed interest and importance of cancer immunotherapy is that James Allison was awarded the Lasker-DeBakey Clinical Research Award in 2015 for his discovery that antibody blockade of CTLA-4 enhances the immune response to cancer. Further, this discovery has stimulated the development of multiple immune checkpoint approaches to the treatment of cancer. In addition, a number of monoclonal antibodies (MAB) have been created to specifically target antigens on cancer cells and/or to selectively deliver radiotherapy to them. These immunotherapeutic approaches and advances will be reviewed in this article.
癌细胞逃避免疫系统的能力是大多数恶性肿瘤最致命的特征之一。因此,近年来开发的针对肿瘤细胞逃避免疫检查点的抗体,如细胞毒性T淋巴细胞相关抗原4(CTLA-4)、程序性细胞死亡蛋白(PD-1)及其配体(PD-L1),已成为治疗和/或根除多种高度恶性癌症的一种主要且显然非常有效的方法。美国食品药品监督管理局(FDA)最近批准了伊匹单抗(靶向CTLA-4)和派姆单抗(靶向PD-1)用于治疗晚期胃癌。事实上,多种检查点阻断抗体已获批准或正在进行临床研究。癌症免疫疗法重新受到关注并凸显其重要性的一个标志是,詹姆斯·艾利森因发现阻断CTLA-4的抗体可增强对癌症的免疫反应,于2015年获得了拉斯克-德巴基临床研究奖。此外,这一发现推动了多种癌症免疫检查点治疗方法的发展。另外,已经制备了一些单克隆抗体(MAB),以特异性靶向癌细胞上的抗原和/或选择性地对其进行放射治疗。本文将对这些免疫治疗方法及进展进行综述。