01020304101201廣義的“基因治療”Cell

Therapy(non-genetically

modified)RNA

TherapyGeneTherapyGeneEditing細(xì)胞治療(未經(jīng)基因改造)基因編輯m

RNA小核酸基因療法

ZFN

TIL

NK

ASO

RNAi

TALEN

/

CRISPR301CAR-T

TCR

T(CAR-T)(TCR-T)(TIL)T(NK)TCRTMHC-TT

CAR-TNature

Reviews2020

859

CARTCAR-T20192904Pubmed01CAR-T/1.2.TTTCAR3.

MHC

CRSCAR-T/C

AR-TCAR-NK/1.2.

NKNK3.

CAR-

NK

NK5Pubmed01TCR-T/1.2.TTTTCR3.

TCRTCRTT4.

MHCMHCTIL/1.2.IL-22

-

310113.OKT3

IL-24.

5-6

6Pubmed01

CARCAR-TCAR

ScFvTTCAR

KymriahYescartaCD19/KiteTecartusBreyanziCD19AbecmaBCMACARVYKTICD19CD19CD19BCMA//KiteBMSBMS/scFvmurinemurinemurineFMC63murineVHH4-1BB4-1BB

(CD137)CD3

zetaCD28CD3

zeta$37.3CD28CD3

zeta$37.34-1BBCD3

zeta$41.04-1BBCD3

zeta1294-1BBTCD3

zeta$41.95CD3

zeta$46.5$47.52017.08(FDA)2017.10(FDA)2020.07(FDA)2021.02(FDA)2021.09(CN)2021.03(FDA)2022.2.28(FDA)7Pubmed02802

CAR-T111CAR-TCAR-TCAR-TTCAR-TCAR-TCAR-T1.5CAR-T0.4CAR-T2(On-Target

Off-Tumor)CAR-TCAR-T3(CRS)2CAR-T3CAR-TCAR-T100~100000CAR-T201737.31000Kymriah

Yes

ca

rtaYescarta/CAR-T4

7.5Kymriah150049Pubmed02CAR-T121312CAR-TCAR-TCAR-T(On-Target

Off-Tumor)34(CRS)2019298.5253.4225.7168.088.782.9

CAR-TCART

CAR-TCAR-TCAR-T

CARscFvNHL79.5

50%

DLBCL68.262.356.736.527.9

CAR10Pubmed02outpatient40~45CAR-T=++4~5evenBreak-

KymriahKymriah47.544%CRSYescarta37.3curetoday

healio1102

2CAR-TFDA2017201820192020202122H12022Q1-32017.08NovartisKymri

a

h676278474587263397yoy1167%2643671%----266%71%24%23%-11%2017.102020.072021.022021.032022.02GileadGileadBMSBMS/YescartaTecartusBreyanziAbecmaCarvykti7-4565636951765061363989-82321712726379yoyyoyyoyyoy73%23%160%82%----44-300%-87164-80%--168%--CAR-T8.236.955.634.565.874.743.972.782.642.631.642.171.761.270.870.760.060.790.440.07KymriahYescartaTecartusBreyanzi2021AbecmaCarvykti20172018201920202022Q1-312031303

2CD19

CAR-TYe

scarta

Breyanzi

2022

CAR-TCAR-TC

AR-T

CRCRORRORRCR

CRS

NTCAR-TCAR-TOutpatient14Pubmed03

2BCMA

CAR-TPubmed1503

2CAR-TTecartusYescartaCD19R/R

Adult

ALLPediatric

ALLZUMA-3ZUMA-42021.10

(FDA)B()

ZUMA-25ZUMA-1CD193L

R/R

LBCL3L+

FL2017.10(FDA)2021.03(FDA)2022.04

(FDA)ZUMA-5ZUMA-72L

R/R

LBCL2L

LBCL

Outpatient

ZUMA-2422H2

FPI1LLBCLFLZUMA-2322H2

FPI19Q1

FPI22H2

FPI1L

LBCL2L+ZUMA-12ZUMA-22BreyanzBMSCD19CD193L+

LBCL2L

LBCL3L+

FL3L+

CLL3L+

MZL3L+

MCL3L+

LBCL3L+

FL3L+

MCLTRANSCENDTRANSFORMTRANSCEND

FLTRANSCEND

CLL2021.02(FDA)2022.06(FDA)20232023RELIANCERELIANCE2021.09(CN)2022.10(CN)JPM2023.02.011603

2CAR-TAbecmaBMSBCMA

5L+

RRMMKarMMa2021.03(FDA)2022.02(FDA)3-5L

MMKarMMa-319Q2FPI2023202322Q41L

MMKarMMa-91L,

2L,

4L+

MMKarMMa-2Cartitude-1Cartifan-118Q4FPI,

22ASHCarvyktiBCMA

RRMMRRMMNDA2-4L

RRMM1L

MMCartitude-4Cartitude-5Cartitude-6Lummica