常见的免疫检查点抑制剂在肿瘤免疫治疗中的现状.ppt

Story of Anti-CTLA-4(Ipilimumab) ?intravenous infusions of 10 mg/kg?ipilimumab?or placebo every 3 weeks for four doses, then every 3 months for up to 3 years. 951 stage III cutaneous melanoma with adequate resection of lymph nodes ?ipilimumab (n=475) or placebo (n=476) Story of Anti-CTLA-4(Ipilimumab) Story of Anti-CTLA-4(Ipilimumab) Clinical trials: Non-small-cell lung cancer Prostage cancer Extensive-disease-small-cell lung cancer . . . . PD-1 (CD279) Member of Ig superfamily Inducible expression on T or B cell Deliver inhibition signal Story of B7-H1/PD-1 PD-L1 (B7-H1,CD274) Member of Ig superfamily Constitutive expression on T APC etc Conditionally deliver negative signal Story of B7-H1/PD-1 FACTS B7-H1 is frequently up-regulated on different types of tumor cells, where it inhibits local antitumor T cell responses. PD-1 is expressed on the majority of tumor infiltrating lymphocytes. J. Konishi, K. Yamazaki, M. Azuma, et al. Clin Cancer Res 2004 10:5094 CONCLUSION Tumor cells take B7-H1 as a weapon to disable tumor sensitive T cell in that way tumor cells can suppress immune cell function and escape from immune attack. SOLUTION Blocking B7-H1/PD-1 interaction to protect tumor infiltrating T cell in order to enhance cell immune against tumor. Beginning of the story ——1992，Discover of PD-1 by Tasuku Honjo. ——1999，Chen Lieping group found B7H1, which was later identified ligand of PD-1. ——2000，Gorden J. Freeman reported PDL1, which was found identical to B7H1. ——2014，Receive William B. Coley Award jointly for distinguished research in tumor immunology Story of B7-H1/PD-1 Chen Lieping Tasuku Honjo Gorden J. Freeman Arlene H. Sharpe Story of B7-H1/PD-1 重磅!?美国前总统卡特脑部癌细胞消失，让世界再次聚焦PD-1/PD-L1重磅炸弹！ 2015年12月6日，美国第39届总统吉米·卡特于6日发表声明说，医生在给他做完最近一次脑部MRI后，没有发现此前在他大脑中出现的黑色素瘤转移灶或新的癌细胞。 Story of B7-H1/PD-1 Clinical trials have been conducted in following cancer: Colorectal cancer Melanoma Prostate cancer NSCLC Renal cell c