靶向t细胞共信号的肿瘤免疫治疗研究进展-药学进展.pdfVIP

PROGRESS IN PHARMACEUTICAL SCIENCES 2015,39 9 :659-665 ( ) 659 靶向 T 细胞共信号的肿瘤免疫治疗研究进展 支旺旺，孙超，王淑珍* （中国药科大学生命科学与技术学院，江苏 南京 210009） [ 摘要 ] T 细胞介导的肿瘤免疫至少需要 T 细胞受体和共刺激分子“双信号”参与的学说目前得到了广泛支持。共抑制或共刺激分子提供的 共信号决定了 T 细胞受体信号介导的免疫应答的最终效应。近年来，靶向共抑制分子如 CTLA-4 和 PD-1 开发的抗体药物在临床应用中获 得了巨大成功，使得肿瘤免疫治疗成为最令人瞩目的研究领域，并被美国《科学》杂志评为 2013 年度十大科学突破之首。肿瘤免疫治疗有 望成为与手术、放化疗和靶向治疗并驾齐驱的抗肿瘤主流治疗方案。针对共抑制分子 CTLA-4、PD-1、PD-L1 和共刺激分子 CD137，综述 其发挥免疫调节作用的分子机制及其相关靶向药物在肿瘤治疗方面的最新进展和应用。 [ 关键词 ] 肿瘤免疫治疗；T 细胞共信号；共抑制；共刺激；拮抗剂；激动剂 [ 中图分类号 ] R979.1 [ 文献标志码 ] A [ 文章编号 ] 1001-5094（2015）09-0659-07 Advances in Research on Cancer Immunotherapy Targeting T Cell Co-signalling ZHI Wangwang, SUN Chao, WANG Shuzhen (School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China) [Abstract] It has been widely accepted that T cell-mediated antitumor immunity requires at least two signals from T cell receptor and co- stimulatory molecules. The co-signal provided by co-inhibitory or co-stimulatory molecules determines the final outcome of the immune response mediated by T cell receptor signalling. Recently, great clinical successes have been achieved in drugs targeting co-inhibitory signaling such as CTLA- 4 and PD-1, which makes immunotherapy become the most notable research area and receive the 2013’s Breakthrough of Year award made by the journal Science. Cancer immunotherapy is expected to become a mainstay treatment for cancer in addition to surgery, radiation, chemotherapy, and targeted therapy. In this review, the most important co-inhibitory (CTLA4, PD-1/PD-L1) and co-stimulatory drug targets (CD137), their mechanisms o