Crystal clear: visualizing the intervention mechanism of the PD-1/PD-L1 interaction by two cancer therapeutic monoclonal antibodies

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• 作者：Shuguang Tan ; Danqing Chen ; Kefang Liu ; Mengnan He ; Hao Song ; Yi Shi…
• 关键词：PD ; 1/PD ; L1 interaction ; checkpoint blockade ; molecular basis ; therapeutic antibody
• 刊名：Protein & Cell
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：7
• 期：12
• 页码：866-877
• 全文大小：1223KB
• 刊物主题：Biochemistry, general; Protein Science; Cell Biology; Stem Cells; Human Genetics; Developmental Biology;
• 出版者：Higher Education Press
• ISSN：1674-8018
• 卷排序：7

文摘

Antibody-based PD-1/PD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre-existing T-cell function to modulate antitumor immunity. In this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-1/PD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural information will benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.