ASCO会后-肺癌免疫治疗进展..docx

肺癌免疫治疗 浙江大学附属第一医院肿瘤内科 浙江大学附属第一医院 肿瘤内科 an an The immune system: “ideal” anti-cancer weapon Diverse attac T cells, antiboi natural killers, Precise targg H Can distinguis 'chemical alter Recall After effective immunity can lifetime ActivePeptide vaccine DC vaccine Genetic vaccineCD40IL-2IFNIL-15IL-21 Active Peptide vaccine DC vaccine Genetic vaccine CD40 IL-2 IFN IL-15 IL-21 0X40 Adoptive cell transfer immunotherapy 肿瘤免疫治疗方式 genetic e genetic e T cell cloning The walls of cancer's defenseagainst immune attack Regulatoryi cells Suppres cytokin Immun ^checkpo CTLA-4和PD-1/L1检查点阻E Priming phase Effector phase (lymph node) (peripheral tissue) R bas A. N Engl J Med. 2012;366:2517 2519 Breakthrough or evolution?? Pardoll. Nature Imrr AUxand?r, ?!. AS< AUxand?r, ?!. AS< CLINICAL PRACTICE - 2* rTITVTOL >C LA Ct'PA DP T2 IOPI I i 7EML4-ALK rTITVTO L > C LA Ct'PA DP T2 IOPI I i 7 EML4-ALK 肿瘤药物的发展策略 新单药 后线治疗 多西他赛疗效恒定 EJ 厄罗替 尼 多西他赛 多西他赛 +雷莫芦单抗 Shepherd 2000 46月 7?5月 1年生耗37% Hanna 2004 8.3 月 7.S 1年生存率29.7% Shepherd 2003 4.7月 6.7月 Garon 2014 9.1 月 10.5 月 9.7月（非鳞癌） Reck 2014 7.9 月（v9月PD） 103月（腺癌） 肺癌的免疫治疗 H*22 20 52 134 26 23 81 227 91 57 121 13 63 21? 11 394 219 20 49 181 231ssyf H*22 20 52 134 26 23 81 227 91 57 121 13 63 21? 11 394 219 20 49 181 231 ssyf IMUI05 cccVVI ?肺癌的高频率体细胞突变可能导致其免疫原性増加2 ?靶向于PD-L1/PD-1通路的治疗将会改变肺癌的治疗 '经允许复制于MacriBan Publishers ltd laurence MS, et al Nature: 2013; 499（7457） 214-218xopvnBht 2013 2Chen DS et al.CCR2012 抗PD-1检查点抑制剂临床研发（实 Antibody Molecule Development Stage Nivolumab Fully human IgG4 Approved (US): advanced melar therapy, advanced squamous N Phase in multiple tumors (NSCl HNSCC, GBMf gastric) Pembrolizumab Humanized IgG4 Approved (US): advanced melar therapy Phase in multiple tumors (HNS< bladder, gastric/GE) Pidilizuma b Humanized IgGl Phase II multiple tumors (pancr prostat巳 CNS) AMP-224 Fc-PD-L2 fusion protein Phase I fitPD-Ll检查点抑制剂临床研发（S Antibody Molecule Development Sta< MEDI4736 (durvalumab) Engineered human IgGl Phase III multiple HNS