Table 2.

CAR-cells in clinical trials in CRC.

Type of immunotherapy	Status/Country	Clinical phase	Vaccination strategy	Combination therapy	Main Findings	NCT identifier	Ref
HITM-SURE Anti-CEA CAR-T	Complete/ United States	I	-Autologous PBMCs isolated by leukapheresis, then activated with anti-CD3 antibody for 48 hours. -Post-activation, cells were retrovirally transduced with a construct encoding an anti-CEA scfv-CD28/CD3ζ CAR. -Intravenous infusion (IL-2) (50,000 IU/kg/day) for 4 weeks during the CAR-T infusion period.	Interleukin-2 (IL-2)	-Safe and effective. -23.2 months survival time -Marked fibrosis in the liver tumor specimen while the integrity of the normal liver tissue was preserved. -The tumor microenvironment shifted towards a less immunosuppressive milieu, -The recurrent disease emerged in the liver.	NCT02850536	(101)
HITM-SIR Anti-CEA CAR-T	Complete/ United States	I	-Autologous PBMCs isolated by leukapheresis, then activated with anti-CD3 antibody for 48 hours. -Post-activation, cells were retrovirally transduced with a construct encoding an anti-CEA scfv-CD28/CD3ζ CAR.	-Selective Internal Radiation Therapy (SIRT)   -Interleukin-2	-Well tolerated -No grade (G) 4/5 events - no instances of severe cytokine-release syndrome (CRS) or neurotoxicity - Reduced levels of GM-CSF-R, IDO, and PD-L1 were detected -The median overall survival time is 8 months	NCT02416466	(102)
Anti-CD133-CAR	Complete/ China	I & II	-CAR T cells produced by directly adding anti-CD3 monoclonal antibody OKT3 to whole PBMCs suspended in culture medium containing interleukin (IL)-2 -Lentivirus-mediated CAR transduction was done on day 3 of cell culture. -After transduction, cells were expanded ex vivo in the presence of IL-2 added three times weekly until the specified cell dose achieved.	CART-EGFR therapy and anti-PD-1 antibody	-Safe and effective -The 3-month disease control rate was 65.2% -Median progression-free survival was 5 months. -Repeated cell infusions provide a longer period of disease stability. -NO detectable de novo lesions -Feasibility with controllable toxicities, and effective activity	NCT02541370	(103, 104)
Anti-CEA CAR-T Cells	Unknown/ China	I	-Peripheral blood was collected from patients, and PBMCs were isolated. -PBMCs were activated by immobilized CD3 and CD28 antibodies. -Then T cells were infected with lentiviral vector in plates with polybrene. -After viral transduction, T cells were expanded by IL-2 for approximately 12–14 days to		-Promising efficacy -Stable disease after treatment with CEA CAR-T cells -No CAR-related toxicity.	NCT02349724	(105)
EPCAM CAR-T	Recruiting/ China	I	-PBMCs cultured and activated with CD3 antibodies and interleukin (IL)-2 for 24 h. -T cells were transduced with the concentrated lentiviral. -Transduced cells were cultured with IL-2 for 14 days	Radiofrequency/microwave ablation	-Significant increases in cytokine levels while circulating–tumor cells (CTC) in the blood decreased to 0 between 7 days and 4 weeks post-infusion. -No grade 3 or greater hematologic toxicity. -No dose-limiting toxicities (DLT) were reported. -No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported.	NCT05028933	(106)
CEA CAR-T cells	Recruiting/ China	I	NA	Pretreatment with Fludarabine and Cyclophosphamide	Final data collection for the primary outcome measure is due on May 15, 2024	NCT05396300	NA
Autologous CAR-T/TCR-T Cell	Recruiting/ United states	I & II	NA	Pretreatment with Fludarabine and Cyclophosphamide	Final data collection for the primary outcome measure is one to March 1, 2023	NCT03638206	NA

Not Applicable (NA).