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派姆单抗的非交叉耐药作用机制成功推翻了易普利姆玛。

Pembrolizumab's non-cross resistance mechanism of action successfully overthrown ipilimumab.

机构信息

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia (A Central University), New Delhi 110025, India; Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan 45142, Saudi Arabia.

Hewitt Laboratory of the Ola B. Williams Glaucoma Center, Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, Charleston, SC 29425, USA.

出版信息

Crit Rev Oncol Hematol. 2017 Mar;111:1-6. doi: 10.1016/j.critrevonc.2017.01.001. Epub 2017 Jan 7.

Abstract

The incidences of melanomas are increasing by leaps and bounds across the globe despite early detection and intervention. The numbers of patients dying from metastatic melanoma have been continually increased over the past thirty years. It has been considered as one of the most therapy-resistant malignancies due to the cross-resistant mechanism developed by the metastatic cells. With time, many new therapies came and they failed miserably. Ipilimumab, a monoclonal antibody that works to activate the immune system by targeting CTLA-4 proved to be a boon for advance melanoma very recently. But it could not stand firmly against the resistant metastatic skin cancer cells. Now, the new skin cancer drug named pembrolizumab proved as a new miraculous molecule. It's a humanized monoclonal antibody that blocks a biological pathway called programmed cell death-1 (PD-1), which melanoma cells activate to suppress the immune system. This antibody has surpassed ipilimumab at all the stages of clinical trials because of its non-cross resistant mechanism to malignant cells. The present review critically analyses the reasons of efficacy success of pembrolizumab over ipilizumab shown at various stages of clinical trials.

摘要

尽管早期检测和干预,黑色素瘤的发病率在全球范围内仍呈突飞猛进的增长。过去三十年来,死于转移性黑色素瘤的患者人数一直在持续增加。由于转移性细胞形成的交叉耐药机制,它被认为是最具耐药性的恶性肿瘤之一。随着时间的推移,许多新的治疗方法相继出现,但都以惨败告终。Ipilimumab 是一种单克隆抗体,通过靶向 CTLA-4 激活免疫系统,最近被证明对晚期黑色素瘤有很大的帮助。但它无法有效地对抗耐药性转移性皮肤癌细胞。现在,一种名为 pembrolizumab 的新型皮肤癌药物被证明是一种新的神奇分子。它是一种人源化单克隆抗体,可阻断一种称为程序性细胞死亡-1(PD-1)的生物途径,黑色素瘤细胞通过该途径激活来抑制免疫系统。由于其对恶性细胞没有交叉耐药机制,这种抗体在临床试验的所有阶段都超过了 ipilimumab。本综述批判性地分析了 pembrolizumab 在临床试验的各个阶段显示出优于 ipilizumab 的疗效成功的原因。

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