Table 3.

Interim results of clinical trials of CD22 CAR-T cells

Clinical trial information	Institution	Transduction/costimulatory domain/scFv (CAR-T product or manufacture procedure)	Disease and patients	Prior CD19 CAR-T	CD19 negative or dim	Dosage	Pharmacokinetics	ORR(≥ CR, best response)	Prognosis	CRS at any grade (grade ≥ 3), evaluation criteria	Neurotoxicity at any grade (grade ≥ 3), evaluation criteria
Phase 1 NCT02315612 [20]	NCI	Lentivirus/4-1BB/m971	R/R B-ALL 21 pts	71.4%	47.6%	0.3 × 106 cells/kg 1 × 106 cells/kg 3 × 106 cells/kg	Peak on D14, persist up to 18 mos	57% (57%)	-	76% (0%) Lee criteria	37.5% (0%) in first 16 patients
Phase 1 NCT02315612 [24]	NCI	Lentivirus/4-1BB/m971 (CD4/CD8 TCS)	R/R B-ALL 57 pts R/R DLBCL 1 pt	62%	56.9%	0.3 × 106 cells/kg 1 × 106 cells/kg 3 × 106 cells/kg	Peak on D14—D21, higher in those at CD4/CD8 TCS cohort	71.9% (70.2%) in evaluable 57 pts	mRFS (CR) 6.0 mos mOS (CR) 13.4 mos	86.2% (8.6%) Lee criteria	32.8% (1.7%) ASTCT criteria
Phase 1 ChiCTR-OIC-17013523 [21]	Beijing Boren Hospital	Lentivirus/4-1BB/- (YK-CD22BB-002)	R/R B-ALL 34 pts	91%	41.2%	0.2 ~ 34.7 × 105 cells/kg	Peak on D12—D15 median persistence time was 28 days by FCM	81.3% (78.1%) in 32 evaluable pts	-	91.2% (2.9%) Lee criteria	17.6% (0%) CTCAE criteria
Phase 1 ChiCTR2000028793 [31]	Beijing Boren Hospital	Lentivirus/4-1BB/- (CD22-CARFH80)	R/R B-ALL 8 pediatric pts	100%	12.5%	0.68 ~ 9.4 × 106 cells/kg	Peak on D11- D15	87.5% (75%)	-	87.5% (12.5%) ASTCT criteria	ICANS 25% (12.5%) ASTCT criteria
Two pilot studies NCT02650414 and NCT02588456 [81]	UPenn/Children’s Hospital of Philadelphia	Lentivirus/4-1BB/m971 (CART22)	R/R B-ALL 3 adult pts / 5 pediatric pts	25%	75%	39.6 ~ 500 × 106 cells/pt	2 CR pts showed significant CAR-T expansion within D20	50% (50%)	-	75% (12.5%) Penn criteria	-
Phase 1 PLAT-07(NCT04571138) [25]	Seattle Children's Hospital	- /4-1BB/m971 (SCRI-CAR22v2)	R/R B-ALL 3 pts	100%	66.7%	2 × 105 cells/kg	-	100% (100%)	-	-	-
New Treatment Measure Clinical Study ChiCTR1800019298 [26]	Tianjin First Central Hospital	-/4-1BB/-	R/R B-ALL 6 pts R/R DLBCL 7 pts	100%	33.3% (B-ALL)	DLBCL: 2.11 ± 0.24 × 106 cells/kg B-ALL: 2.07 ± 0.42 × 106 cells/kg	Peak on D14	DLBCL: 85.7% (57.1%) B-ALL: 33.3% (33.3%)	-	DLBCL: 42.9% (0%) B-ALL: 100% (16.7%) Lee criteria	ICANS 0% (0%) ASTCT criteria
Phase 1 NCT04150497(BALLI-01) [27]	Cellectis S.A	Lentivirus/4-1BB/- (UCAR-T22, disruption of TRAC and CD52 genes using TALEN technology)	R/R B-ALL 3 pts	33.3%	-	~ 1 × 106 cells/kg	Peak on D9—D14	66.7% (33.3%)	-	33.3% (0%)	0% (0%)
Phase 1 NCT04088890 [28]	Stanford University School of Medicine	Lentivirus/4-1BB/m971 (CD4/CD8 T selection)	R/R LBCL 3 pts	100%	66.7%	1 × 106 cells/kg	Peak on D14, persist up to 3 mos by qPCR	100% (100%)	-	100% (0%) ASTCT criteria	ICANS 0% (0%) ASTCT criteria
Phase 1 NCT04088890 (cohort expansion) [29]	Stanford University School of Medicine	Lentivirus/4-1BB/m971	R/R LBCL 21 pts	95%	-	1 × 106 cells/kg 3 × 106 cells/kg	Peak on D14	85.7% (66.7%)	mPFS not reached mOS not reached	100% (4.8%) ASTCT criteria	ICANS 19% (0%) ASTCT criteria
Phase 1 NCT02650414 [30]	UPenn	Lentivirus/4-1BB/m971 (CART22-65 s)	R/R B-ALL 17 pts	94.1%	100.0%	0.8 ~ 10 × 106 cells/kg (3—day fractionated dosing)	Peak on D20	76.5% (76.5%)	mRFS 5.3 mos mEFS 5.8 mos mOS 16.5 mos	88.2% (0%)	35.3% (0%)

NCI National Cancer Institute, UPenn University of Pennsylvania, TCS T-cell selection, UCAR-T universal chimeric antigen receptor T-cell, TRAC T- cell receptor alpha constant, TALEN transcription activator-like effector nuclease, R/R refractory or relapsed, ALL acute lymphocyte leukemia, LBCL large B cell lymphoma, FCM flow cytometry, ORR overall response rate, CR complete response, mos months, qPCR quantitative real-time polymerase chain reaction, mPFS median progression-free survival, mRFS median relapse-free suvival, mEFS median event-free survival, mo months, mOS median overall survival, NE not evaluated, CRS cytokine release syndrome, ASTCT American Society for Transplantation and Cellular Therapy, CTCAE Common Terminology Criteria for Adverse Events, ICANS immune effector cell-associated neurotoxicity syndrome