免疫检查点抑制剂在肿瘤免疫治疗中的现状课件.ppt

Story of Anti-CTLA-4(Ipilimumab) Time table of the long adventure ——1987，Discover of CTLA-4. Nature?1987 328, 267-270 ——1996，James Allison published a paper in Science showing that CTLA-4 antibodies erased tumors in mice. ——1999，Medarex acquired rights to the antibody, taking the leap from biology to drug. ——2010，BMS published a report in NEJM of anti CTLA-4 antibody ipilimumab treatment for metastatic melanoma. ——2011, the U.S. FDA approved Bristol-Myers Squibb’s anti–CTLA-4 treatment for metastatic melanoma. ——2012，Steve A. Rosenberg group published a long term follow up report in CCR of ipilimumab treatment for metastatic melanoma. James P. Allison YERVOY(iplimumab) by Bristol-Myers Squibb Fully humanized antibody Binding to CTLA-4 Blocking B7/CTLA-4 interaction Story of Anti-CTLA-4(Ipilimumab) Story of Anti-CTLA-4(Ipilimumab) 676例HLA-A*0201–阳性有不可切除的III或IV期黑色素瘤患者，其疾病已进展正在接受对转移疾病治疗， 接受Ipilimumab加gp100(403例患者) 单独ipilimumab(137例) 或单独gp100(136例) N Engl J Med 2010;363:711-23. Ipilimumab剂量3 mg/kg体重，每3周1次直至四次治疗(诱导)。 Story of Anti-CTLA-4(Ipilimumab) N Engl J Med 2010;363:711-23. Story of Anti-CTLA-4(Ipilimumab) N Engl J Med 2010;363:711-23. 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 anti