Chimeric antigen receptor T cell therapy: Revolutionizing cancer treatment

Table 4 Emerging target antigens for chimeric antigen receptor T cell therapy

Target specific CAR-T	Targeted cancer	Prominent clinical trials	Trial phase	Study outcome	Ref.
Hematologic cancers
CD20-CAR	Leukemias and lymphomas (e.g., R/R B-NHL)	NCT03277729, NCT04007029, NCT04697940, NCT01735604	Phase 1/2	NCT03277729: High CR+, ORR+ and safety profile; NCT01735604: 54.55% CR+, 18.18% SD+, 180 days median PFS	[88]
CD22-CAR	Leukemias and lymphomas (e.g., R/R B-ALL)	NCT03262298, NCT05470777, NCT055078227, NCT04088890	Phase 1/2	NCT03262298: Dose-reliant anti-tumor effect; NCT04088890: 100% CR+ effect in CD19-treated recurrence	[89]
CD30-CAR	R/R Hodgkin’s lymphoma	NCT02690545, NCT02917083	Phase 1/2	59% CR+; 72% ORR; high safety profile	[90]
NKG2D-Ligand based CAR	R/R- (TLL, AML, MDS)	NCT02203825	Phase 1	High antitumor efficacy	[91]
CD33-CAR	R/R AML	NCT03971799	Phase 1/2	Not completed	[92]
CD123-CAR	R/R AML	NCT04014881	Phase 1	Not completed	[92]
CLL-1.CD33 and/or, CD123-CAR	R/R AML	NCT04010877	Phase 1/2	Not completed	[92]
FLT3-CAR	R/R AML	NCT05023707	Phase 1/2	Strong anti-tumor effect and low OT/OT toxicity	[93]
IL-1RAP-CAR	CML	NCT02842320	Phase 1	Anti-leukemic cytotoxicity against antigen expressing cells	[94]
CD7-CAR	R/R TLL	NCT04689659	Phase 1/2	Effective in vivo CAR-T cell expansion, High CR+, feasible safety profile	[95]
CD4-CAR	R/R T-cell lymphoma	NCT04712864	Phase 1	Powerful anti-tumor cytotoxicity	[96]
CD38-CAR	R/R AML	NCT04351022	Phase 1/2	66.7% CR+, 240 days OS	[97]
CD5-CAR	R/R T-cell lymphoma	NCT03081910	Phase 1	Moderate response and safety profile	[98]
Solid cancers
HER2-CAR	CNS tumor	NCT03500991	Phase 1	Specially localized immune response	[99]
HER2-CAR	HER2+ breast, gastric, pancreatic cancer	NCT04650451, NCT04430595	Phase 1/2	NCT01935843: 4.5 month of PR+, 45.45% SD+, 146 days median PFS+	[100]
Allogenic NKG2D-CAR (CYAD-101)	mCRC	NCT03692429, NCT04991948	Phase 1	NCT03692429: 13.33% CR+, 60% SD, 46.67% with quarterly SD and 119 days median PFS	[101]
IL13Rα2-CAR	Glioblastoma	NCT04003649, NCT04661384, NCT02208362, NCT01935843	Phase 1	NCT01935843: Tumor shrinkage maintenance for 7.49 months; but antigen downgrading based tumor re-occurrence	[29]
GPC3-CAR	HCC	NCT03198546, NCT02395250, NCT03146234	Phase 1/2	NCT02395250 and NCT03146234: 18.18% PR+, highest 3.68 years OS+, 50.3% and 10.5% OS+ rate in 6 and 36 months	[85]
EGFR806-CAR	Advanced solid tumors	NCT03618381	Phase 1	Not completed	[92]
MUC1/PD-1-CAR	NSCLC	NCT03525782	Phase 1/2	Not completed	[92]
GD2-CAR	Brain cancer	NCT04099797	Phase 1	Enrolling participants	[92]
Mesothelin-CAR	Lung, pancreatic, ovarian, and cervical cancer	NCT01583686	Phase 1/2	Enrolling participants	[92]
CEA-CAR	Lung, colorectal, breast, stomach, and pancreatic cancer	NCT02349724	Phase 1	Enrolling participants	[92]
CD19.B7H3-CAR	Advanced solid tumors	NCT04483778	Phase 1	Enrolling participants	[92]
TnMUC1-CAR	R/R solid tumors	NCT04025216	Phase 1	Not completed	[92]

ALL: Acute lymphoblastic leukemia; AML: Acute myeloid leukemia; B-NHL: B-cell non-Hodgkin’s lymphoma; TLL: T-cell acute lymphocytic leukemia; AML: Acute myeloid leukemia; OT/OT: On-target/off-tumor; MDS: Myelodysplastic syndrome; AML: Acute myeloid leukemia; CML: Chronic myelogenous leukemia; CNS: Central nervous system; HER2: Human epidermal growth factor receptor 2; mCRC: Metastatic colorectal cancer; CR: Complete remission; CNS: Central nervous system; HCC: Hepatocellular carcinoma; NSCLC: Non-small cell lung cancer; ORR: Overall response rate; OS: Overall survival; PR: Partial response; PFS: Progression-free survival; R/R: Relapsed/refractory; SCLC: Small-cell lung cancer; SD: Stable disease; MUC1: Mucin-1; CAR: Chimeric antigen receptor.