1、CAR-T TCR-T T TCR-T CAR-T CAR-T T T T T CAR-T clinical.gov CAR-T 282 CAR-T “ ” Carl H June T 2017-01-09 Armstrong 1956 E. Donnall Thomas GVHD 1990 1979 GVHD E. Donnall Thomas 2002 NCI Steven Rosenberg TIL TIL 8 50% TIL Steven Rosenberg T TIL TIL MART-1 gp100 T T TCR-T Steven Rosenberg 2 TIL DMF4 DMF
2、5 MART-1/HLAA*02 (A2 ) T DMF4 TCR TIL 2006 12 2 TIL T TCR TCR DMF4 TCR MART-1 DMF5- TCR 30% 6/20 TCR DMF5-TCR MART-1 MART-1 TCR-T CEA NY-ESO-1 MAGE TCR-T Robbins NY-ESO-1 TCR-T 55% 11/20 61% 11/18 “ ” Carl H June NY-ESO-1 TCR-T 80% 16/20 2016 TCR-T NCI CEA TCR-T 3 1 3 - CEA MAGE TCR-T 3 NCI MAGE-A3
3、3 2 TCR MAGE-A3 MAGE-A9 MAGE-A12 T MAGE-A12 TCR MAGE-A3 TCR-T 2 1 TCR 2 T MAGE-A3 MAGE-A3 TCR -Titin MAGE-A3 TCR TCR-T TCR-T HPV CAR-T TCR-T CAR-T T CAR CAR-T Zelig Eshhar Zelig Eshhar Zelig Eshhar T TCR scFv CAR-T CAIX CAR-T CAR-T CAR-T 2008 Baylor Malcolm Brenner GD2 CAR-T 24 CAR-T 0.1% 11 3 CAR-T
4、 CAR-T 4-1BB CD28 Bcl-xL T T CAR-T 2 CAR-T HER2 CAR-T HER2 40 NCI HER2 scFv CAR-T HER2+ CAR-T 1*10 11 X 5 CAR-T HER2 T CD19 HER2 CAR-T CAR-T CAR-T CD19 CD20 B CD20 CD19 CAR-T 2007 2008 2009 Michel Sadelain Baylor Carl H June Steven Rosenberg NCI CD19 CAR-T 2010 Steven Rosenberg James Kochenderfer CD
5、19 CAR-T CD28 CAR-T FL 8 6 5 CAR-T PBMC 1% 10 0.01% Michel Sadelain教授 2011 Carl H June 4-1BB CD19 CAR-T CLL CAR-T 8 CAR-T 1.42*10 7 10 9 10 11 2-3 Carl H June教授 2011 Renier Brentjens Michel Sadelain Baylor CD28 CD19 CAR-T CLL ALL 10 7 /kg 24h 1 1 CLL 6 1 ALL 2 CAR-T CAR-T FL CLL ALL B MM B CD19 B 20
6、15 Carl H June Alfred Garfall Edward Stadtmauer 1 4-1BB CD19 CAR-T 43 9 CAR-T 95% MM 99.95% B CD19 CAR- T 5*10 7 100 0.05% CD19 B CD19 CAR-T CD19 CD19 CAR-T CD19 CD138 BCMA CD33 CD123 AML CAR-T T IL-1 IL-2 IL-6 IL-8 Cytokine release syndrome CRS Emily Whitehead CAR-T ALL CAR-T Emily Emily ALL CAR-T
7、Emily 5 ICU Emily IL-6 Emily IL-6R Emily Emily 11 CAR-T治愈的儿科患者 Emily Whitehead CRS Juno CAR-T JACR015 2015 2 “ ” CAR-T CAR-T 2013 年，Fred Hutchinson 、纪念斯隆 凯特琳癌症中心和西雅图儿童医院的科学家联手成立了Juno 。 宾大携手诺华开发CAR-T疗法，Kite则与NCI合作。礼来、葛兰素史克、强生、默克通过投资介入CAR-T领 域。其他的CAR-T研发型企业包括BlueBird、Bellicum、Cellectis等，后文将一一介绍其技术特点。
8、CAR-T CAR-T / CAR-T 2 1 19 CAR-T Steven Rosenbergs NCI 10 7 HER2 CAR-T HER2 CAR-T Baylor 19 10 4 10 8 NCI 3 mesothelin CAR-T 2 1 1 CAR-T CD19 CAR-T CAR-T HER2 CAR-T T MART-1 gp100 CEA glioblastomamultiforme 15 EGFRvIII CAR-T EGFRvIII EGFR EGFRvIII EGFRvIII EGFR scFv Carl H June 4-1BB EGFRvIII CAR-T
9、NCI Steven Rosenberg 4-1BB CD28 EGFRvIII CAR-T EGFRvIII CAR-T TCR-T疗法、CAR-T疗法临床研究一览 IL13R2 CAR-T city of hope Michael Jensen IL13R2 scFv IL13 Zetakine IL13R2 2015 13 GBM DNA 3-4 3 CAR-T 3 CAR-T mesothelin cMet MUC1 GD2 EphA2 EGFR CD171 CD133 CAR-T FAP VEGFR2 CAR-T “ ” TCR-T TCR CARTCR MHC-Peptide mo
10、l scFv nmol NCI MART-1 TCR-T DMF5 TCR 30% DMF4 TCR 13% scFv TCR MHC-peptide 3 EGFRvIII scfv 101nM NCI EGFRvIII scFv 0.58nM 2015 Yangbing Zhao MD Anderson Cancer Center Laurence Cooper 2015 Ziopharm CEO Cancer Research anti-HER2 scFv CAR-T “sweet spot ” Baylor HER2 CAR-T 19 Yangbing Zhao教授 CAR-T RNA CAR HER2 CAR-T CAR-T Carl H June CAR RNA RNA T CAR 7 GBM T 2016 12 29 Michael Jessen 1 50 IL13R2 CAR-T IL13R2 CAR-T Baylor NCI HER2 CART 10 11 Baylor NCT02442297 10 7 10 8 HER2 Bucket trial 10 4 Baylor T scFv NCI gp-100 TCR HAMA CD19 CAR-T CAR-T B B CAR-T CAR-T CAR-T
