Table 5.

Results of clinical trials of CD19/CD22 dual-targeting CAR-T cells

Clinical trial information	Institution	Dual-targeting strategy	CAR structures	Disease and patients	Prior CD19 CAR-T treatment at baseline	ORR(≥ CR, best response)	Prognosis	CRS at any grade (grade ≥ 3), evaluation criteria	Neurotoxicity at any grade (grade ≥ 3), evaluation criteria
Observational study ChiCTR-OPN-16008526 [86]	Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology	Sequential infusion without interval (D0-D3)	anti-CD19 scFv (Murine)/4-1BB anti-CD22 scFv (Murine)/4-1BB	R/R B-ALL 51 pts R/R B-cell NHL 38 pts	-	B-ALL: 98% (96%) in 50 evaluable pts B-cell NHL: 72.2% (50%) in 36 evaluable pts	B-ALL: mPFS 13.6 mos, mOS 31 mos B-cell NHL: mPFS 9.9 mos, mOS 18 mos	95.5%(17.9%) Lee criteria	CRES 13.5% (1.1%) CTCTE criteria
Observational study ChiCTR-ONC-17013648 [87]	Beijing Boren Hospital	Sequential infusion	FMC63 scFv/4-1BB anti-CD22 scFv (human)/4-1BB	R/R B-ALL 21 pts	100% (16 CR, 3 PR, 2 relapsed)	95% (95%)	18-month OS rate 88.5% 18-month EFS rate 67.5%	52% (0%) Penn criteria	0% (0%) CTCTE criteria
Phase 1 ChiCTR-OIB-17013670 [88]	Beijing Boren Hospital	Sequential infusion	anti-CD19 scFv/4-1BB anti-CD22 scFv/4-1BB	R/R B-ALL 20 pts	-	100% (100%)	mLFS/mOS not reached 1-year LFS rate 79.5% 1-year OS rate 92.3%	CD19 CAR-T 90% (5%) CD22 CAR-T 75% (0%)	CD19 CAR-T 15% (5%) CD22 CAR-T 15% (0%)
Phase 2 ChiCTR2000032211 [89]	Multicenter	Coadministration (1:1)	anti-CD19 scFv/4-1BB anti-CD22 scFv/4-1BB	B-ALL 6 pts R/R B-ALL 188 pts B-ALL with isolated EMD 31 pts	-	99% (99%)	12-month EFS rate 73.5%	88% (28.4%) ASTCT criteria	20.9% (4.0%) ASTCT criteria
Phase 1 NCT03289455 [93]	Autolus PLC	Bicistronic CAR-T	FMC63 scFv/OX40 LT22 scFv-COMP/4-1BB	R/R B-ALL 15 pts	-	86.7% ( 86.7%)	-	80% (0%) Lee criteria	ICANS 26.7% (0%) ASTCT criteria
Phase 1 (UCAR-T) NCT04227015 [95]	The First Affiliated Hospital, School of Medicine, Zhejiang University	Tantem CAR-T	FMC63 scFv-m971 scFv/4-1BB	R/R B-ALL 6 pts	-	83.3% (83.3%)	-	100% (16.7%)	0% (0%)
Phase 1 ChiCTR1800015575 [96]	The First Affiliated Hospital, School of Medicine, Zhejiang University	Tantem CAR-T	FMC63 scFv-anti-CD22 scFv(human)/4-1BB	R/R B-cell lymphoma 16 pts	-	87.5% (62.5%)	2-year OS rate 77.3% 2-year PFS rate 40.2% mPFS 246 days	100% (6.3%) ASTCT criteria	0% (0%) CTCAE criteria
Phase 1 NCT03185494 [97]	Institute of Basic Medicine, Chinese PLA General Hospital	Tantem CAR-T	m971 scFv-FMC63 scFv/4-1BB	R/R B-ALL 6 pts	-	100% (100%)	-	100% (0%) Lee criteria	ICANS 0% (0%) ASTCT criteria
Phase 1 NCT03233854 [102]	Stanford University School of Medicine	Loop CAR-T	FMC63 VH-m971 VL-m971 VH-FMC63 VL/4-1BB	R/R B-ALL 17 pts R/R LBCL 21 pts	DLBCL 65%	B-ALL: 100% (80%) LBCL: 62% (29%)	-	76% (5%) Lee criteria	37% (10.5%) CTCAE criteria
Phase 1 NCT03919526 [103]	Shanghai General Hospital, Shanghai Jiaotong University School of Medicine	Loop CAR-T	FMC63 VL-m971 VH-m971 VL-FMC63 VH/4-1BB	B-ALL 15 pts	-	100% (100%)	mRFS/mOS not reached 12-month RFS rate 77% 12-month OS rate 86%	26.7% (0%) ASTCT criteria	ICANS 0% (0%) ASTCT criteria

PLA Liberation Army General, UCAR-T universal chimeric antigen receptor T-cell, R/R refractory or relapsed, ALL acute leukemia lymphocyte, CR complete response, pt patient, NHL non-Hodgkin lymphoma, PR partial remission, ORR overall response rate, mPFS median progression-free survival, mOS median overall survival, EFS median event-free survival, mos months, mLFS median leukemia-free survival, mRFS median relapse-free suvival, mos months, CRS cytokine release syndrome, ICANS immune effector cell-associated neurotoxicity syndrome, ASTCT American Society for Transplantation and Cellular Therapy, CTCAE Common Terminology Criteria for Adverse Events