Table 4. Clinical trials based on the application of CRISPR-Cas9 strategy for improving ‎the efficacy of CAR-T cell .

Rank	Clinical Trial identifier	Status	Clinical trial phase	Disease	CAR Antigen	Target Locus of CRISPR	NK source	Number enrolled	Interventions	Dosage	Starting date	Location
1	NCT03166878	Unknown	Phase 1/2	CD19+ leukemia and lymphoma	CD19	Endogenous TCR and B2M genes	Allogeneic	80	Universal CRISPR-Cas9 Gene-Editing CAR-T Cells Targeting CD19	Unknown	June 2017	China
2	NCT03398967	Unknown	Phase 1/2	B-cell malignancies	CD19, and CD20 or CD22	Unknown	Allogenic	80	Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cells	Unknown	January 2, 2018	China
3	NCT03545815	Unknown	Phase 1	Solid Tumors	Mesothelin	PD-1 and TCR gene-knocked out	Unknown	10	anti-mesothelin CAR-T cells	Unknown	March 19, 2018	China
4	NCT03747965	Unknown	Phase 1	Solid Tumors	Mesothelin	PD-1 gene-knocked out	Unknown	10	Mesothelin-directed CAR-T cells	Unknown	November 2018	China
5	NCT05812326	Completed	Phase 1/2	MUC1-positive breast cancer	MUC1	PD-1	Autologous	15	AJMUC1- PD-1 gene knockout anti-MUC1 CAR-T cells	3×105/kg, 1×106/kg 3×106/kg	May 17, 2019	China
6	NCT04035434	Recruiting	Phase 1	B-cell malignancies	CD19	Unknown	Allogenic	143	CD19-directed CAR-T-cell (CTX110)	Unknown	July 22, 2019	Unknown
7	NCT04037566	Recruiting	Phase 1	CD19+ leukemia or lymphoma	CD19	Endogenous HPK1	Autologous	40	CD19-specific CAR-T cells with edited endogenous HPK1 (XYF19 CAR-T cells)	Unknown	August 2019	China
8	NCT04438083	Active, not recruiting	Phase 1	Renal Cell Carcinoma	CD70	Unknown	Allogeneic	107	CRISPR-Cas9-Engineered T Cells (CTX130)	Unknown	June 16, 2020	USA
9	NCT04502446	Recruiting	Phase 1	T or B cell malignancies	CD70	Unknown	Allogeneic	45	Anti-CD70 CRISPR-Cas9-Engineered T Cell	Unknown	July 31, 2020	USA
10	NCT04557436	Active, not recruiting	Phase 1	B-ALL	CD19	CD52 and TRAC loci	Allogenic	10	CRISPR-CAR Genome Edited T Cells (PBLTT52CAR19)	Unknown	August 12, 2020	UK
11	NCT04767308	Not yet recruiting	Early phase 1	CD5+ Hematopoietic Malignancies	CD5	Unknown	Autologous	18	Anti-CD5 CAR-T Cells	1×106/kg 2×106/kg 3×106/kg	March 2021	Unknown
12	NCT04637763	Recruiting	Phase 1	B cell non-Hodgkin lymphoma	CD19	Unknown	Allogeneic	72	CRISPR-edited allogeneic CAR-T cell therapy targeting CD19	Unknown	May 26, 2021	USA
13	NCT04976218	Recruiting	Phase 1	EGFR positive solid tumors	EGFR	TGF-β receptor Ⅱ	Unknown	30	TGFβR-KO CAR-EGFR T Cells	1-2×105/kg 1×106/kg 1×107/kg	March 15, 2022	China
14	NCT05397184	Recruiting	Phase 1	T Cell Malignancies	CD7	Unknown	Allogeneic	10	Cryopreserved BE CAR7 T cells	Unknown	April 19, 2022	UK
15	NCT05037669	Withdrawn	Phase 1	CD19+ Leukemia and Lymphoma	CD19	Endogenous TCR, HLA-class I and HLA-class II	allogeneic	0	CRISPR-edited T Cells (PACE) Gene Edited to Eliminate Endogenous TCR, HLA-class I and HLA-class II and Engineered to Express Anti-CD19 CAR	Unknown	July 2022	Unknown
16	NCT05722418	Recruiting	Phase 1	Multiple myeloma	BCMA	Unknown	allogeneic	50	CRISPR-Edited Allogeneic Anti-BCMA CAR-T Cell	Unknown	February 6, 2023	USA
17	NCT05643742	Recruiting	Phase 1/2	B-cell malignancies	CD19	Unknown	allogeneic	120	Anti-CD19 Allogeneic CRISPR-Cas9-Engineered T Cells (CTX112)	Unknown	March 10, 2023	USA
18	NCT05795595	Recruiting	Phase 1/2	Solid tumors	CD70	Unknown	allogeneic	250	Anti-CD70 Allogeneic CRISPR-Cas9-Engineered T Cells (CTX131) i	Unknown	April 2023	USA