肺癌免疫治療進(jìn)展

1、晚期肺癌免疫治療浙江大學(xué)附屬第一醫(yī)院腫瘤內(nèi)科the immune system:最佳武器 w 一多樣 精確持久an “ideal anti-cancer weapondiverse attackt cells, antibodies, natural killers, etc.pre!sejargetcan distinguish minute；chemical alterations力 recalla after effective priming, i immunity can last for a lifetime腫瘤免疫治療方式repiiae vaccine二dc vaccine.ge

2、netic vaccine-一% 7active immunotherapyadoptive cell transfer1immunotherapyt cell cloningcd40 j0x40_|w =pd tcr or car genetic engineering癌癥抵御免疫調(diào)節(jié)抑制檢查點(diǎn)the walls of cancers defenseagainst immune attackregulatory immunecellssuppressivecytokinesimmune“checkpoints”ctla-4和pd-1/l1檢查點(diǎn)阻斷priming phase (lymph n

3、ode)effector phase (peripheral tissue)ribas a. n engl j med. 2012;366:2517-2519.breakthrough or evolution?ctla-4cloning ofctla-4 genetdemonstration of organ-specific autaimmunity inpd-1 ko mkepd-l1 expression intrurine tumors confers immune resistances high pd-li expression inhuman tumorsfi r st d &

4、 m o n st rat b a n of cltnka! activity of anti-pd-lcloningolpd-1pd-l1/pd-l2identified aspd-1 ligandspnti-po-l jpredictedfda approval of antb-pd-1anti-pol&anthpoll induce durable tumor responses in melanoma, kidney & lung cancerpardoli, nature immunoi 2012clinical practice - 2015ros1i sti tutu nziom

5、ale per lo studioe li. cura dei tur.lorii zjeiited at：annualmeeting腫瘤藥物的發(fā)展策略二線(xiàn)治療新聯(lián)合化療一線(xiàn)治療新單藥后線(xiàn)治療輔助/新輔助多西他賽療效恒定肺癌的高頻率體細(xì)胞突變可能導(dǎo)致其免疫原性增加2靶向于pd-l1/pd-1通路的治療將會(huì)改變肺癌的治療1 經(jīng)允許復(fù)制干machllan publishers ltd lawrence ms, et al. nature: 2013; 499(7457) 214-218.copyright 2013 2chen ds et al.ccr 2012alexander / et al.

6、 asco 2015abstract 8010抗pd-1檢查點(diǎn)抑制劑臨床研發(fā)（實(shí)體瘤）antibodymoleculedevelopment stageapproved (us): advanced melanoma after previousnivolumabfully human igg4therapy, advanced squamous nsclc after ctphase iii multiple tumors (nsclc, melanoma, rccfhnsccf gbm, gastric)approved (us): advanced melanoma after prev

7、iouspembrolizumabhumanized igg4therapyphase iii multiple tumors (hnscc, nsclcf melanoma, bladder, gastric/ge)pidilizumabhumanized igglphase ii multiple tumors (pancreatic, crcf rcc, prostate, cns)amp-224fc-pd-l2 fusion proteinphase i抗pdl1檢查點(diǎn)抑制劑臨床研發(fā)（實(shí)體痛）antibodymoleculedevelopment stagemedi4736 (durvalumab)engineered human igglphase iii multiple tumors (nsclcf hnscc)mpdl3280a (atezolizumab)engineered h