Advances and challenges of chimeric antigen receptor T cell therapy in digestive system malignancies

Table 1 Current clinical trials of chimeric antigen receptor T cell therapy in the gastrointestinal system

Interventions	Tumor type	Sponsor	NCT number
Claudin18.2 CAR-T	Digestive tumors	Shenzhen University General Hospital	NCT05620732
Cadherin 17 CAR-T	Digestive tumors	Chimeric Therapeutics	NCT06055439
Anti-mesothelin T naive/SCM hYP218 (TNhYP218) CAR-T	Digestive tumors	National Cancer Institute	NCT06885697
EpCAM CAR-T	Digestive tumors	Zhejiang University	NCT05028933
NKG2D/CLDN18.2 CAR-T	Digestive tumors	The Affiliated Hospital of the Chinese Academy of Military Medical Sciences	NCT05583201
Binary oncolytic adenovirus + HER2-specific autologous CAR VST	Digestive tumors	Baylor College of Medicine	NCT03740256
CDH17 CAR-T	Digestive tumors	Zhejiang University	NCT06937567
Claudin18.2 CAR-T	Digestive tumors	Suzhou Immunofoco Biotechnology Co., Ltd	NCT05472857
CLDN6 CAR-T	Digestive tumors	BioNTech Cell and Gene Therapies GmbH	NCT04503278
Claudin18.2 CAR-T	Digestive tumors	Legend Biotech USA Inc.	NCT05539430
CEA CAR-T	Digestive tumors	Changhai Hospital	NCT05240950
A logic-gated MSLN CAR-T therapy with a blocker receptor for HLA-A02	Digestive tumors	A2 Biotherapeutics Inc.	NCT06051695, NCT06682793
MSLN CAR-T	Digestive tumors	UTC Therapeutics Inc.	NCT06256055
MSLN CAR-T	Digestive tumors	CRISPR Therapeutics AG	NCT05795595
IL15 armored GPC3 CAR-T	Digestive tumors	Baylor College of Medicine	NCT05103631, NCT04377932
IL15 and IL21 armored GPC3 CAR-T	Digestive tumors	Baylor College of Medicine	NCT06198296, NCT04715191
GPC3 CAR-T	Digestive tumors	Second Affiliated Hospital of Guangzhou Medical University	NCT03198546
Universal CAR-T	Digestive tumors	Wondercel Biotech (Shenzhen)	NCT06653023
MSLN/GPC3/GUCY2C CAR-T	Digestive tumors	Second Affiliated Hospital of Guangzhou Medical University	NCT05779917
CD70 CAR-T	Digestive tumors	National Cancer Institute	NCT02830724
IL13R alpha2-specific hinge-optimized 4-1BB-co-stimulatory CAR	Digestive tumors	Jonsson Comprehensive Cancer Center	NCT04119024
CEA CAR-T	Digestive tumors	Chongqing Precision Biotech Co., Ltd	NCT06010862, NCT05415475, NCT06821048, NCT06126406, NCT06006390, NCT06043466
Irradiated PD-L1 CAR-NK cells plus pembrolizumab plus N-803	GC	National Cancer Institute	NCT04847466
Claudin18.2 CAR-T	GC	Peking University	NCT06353152
Claudin18.2 CAR-T	CRC	Second Affiliated Hospital, School of Medicine, Zhejiang University	NCT06946615
GUCY2C CAR-T	CRC	Beijing ImmunoChina Medical Science and Technology Co., Ltd.	NCT06718738
Universal CAR-T	CRC	Wondercel Biotech (ShenZhen)	NCT06653010
An armored GUCY2C targeting WD-01 CAR-T	CRC	Wondercel Biotech (ShenZhen)	NCT06675513
LGR5 CAR-T	CRC	Carina Biotech Limited	NCT05759728
Chemotherapy + allogeneic NKG2D CAR-T	CRC	Celyad Oncology SA	NCT03692429
MSLN CAR-T	EC	Memorial Sloan Kettering Cancer Center	NCT06623396
NKG2D CAR-NK cells	HCC	Zhejiang University	NCT07021534
GPC3 CAR-T	HCC	Shanghai Ming Ju Biotechnology Co., Ltd.	NCT06144385
GPC3 CAR-T	HCC	National Cancer Institute	NCT05003895
GPC3 CAR-T	HCC	Shenzhen University General Hospital	NCT05620706
GPC3 CAR-T	HCC	Renji Hospital	NCT05926726
B7H3 CAR-T	HCC	The Affiliated Hospital of Xuzhou Medical University	NCT05323201
GPC3 CAR-T	HCC	Zhejiang University	NCT06461624
IL-18 armored GPC3-CAR-T	HCC	Eutilex	NCT05783570
GPC3 CAR-T	HCC	CARsgen Therapeutics Co., Ltd.	NCT06560827
TGF-β receptor II armored GPC3 CAR-T	HCC	Zhejiang University	NCT05155189
GPC3 CAR-T	HCC	OriCell Therapeutics Co., Ltd.	NCT05652920
MSLN and claudin18.2 dual CAR-T	PC	Essen Biotech	NCT07066995
Claudin18.2 CAR-T	PC	CARsgen Therapeutics Co., Ltd.	NCT05911217
MSLN CAR-T	PC	Tianjin Medical University Cancer Institute and Hospital	NCT06760364
B7H3 CAR-T	PC	UNC Lineberger Comprehensive Cancer Center	NCT06158139

NCT: National Clinical Trial; CAR-T: Chimeric antigen receptor T cell therapy; SCM: Stem cell memory; EpCAM: Epithelial cell adhesion molecule; NKG2D: Natural killer group 2 member D; CLDN18.2: Claudin 18 isoform 2; HER2: Human epidermal growth factor receptor 2; CAR: Chimeric antigen receptor; VST: Virus-specific T-cell; CDH17: Cadherin 17; CLDN6: Claudin 6; CEA: Carcinoembryonic antigen; MSLN: Mesothelin; HLA: Human leukocyte antigen; IL: Interleukin; GPC3: Glypican-3; CD70: Cluster of differentiation 70; GUCY2C: Guanylyl cyclase C; IL13R alpha2: Interleukin 13 receptor alpha 2; 4-1BB: 4-1BB receptor; PD-L1: Programmed cell death ligand 1; NK: Natural killer; LGR5: Leucine-rich repeat containing G protein-coupled receptor 5; B7H3: B7 homolog 3; TGF-β: Transforming growth factor beta; GC: Gastric cancer; CRC: Colorectal cancer; EC: Esophageal cancer; HCC: Hepatocellular carcinoma; PC: Pancreatic cancer.