Anti-CEA CAR-T Cells to Treat Colorectal Liver Metastases

Inclusion Criteria:

1. ≥18 years old, ≤75 years old, male or female;
2. Patients diagnosed with liver metastasis of colorectal cancer underwent radicalsurgery for the primary lesion of colorectal cancer, and R0 resection was performedfor the liver metastasis (R0 resection was required for other organ metastasis). Therewas no measurable disease or tumor remnants (except invisible or unmeasurable disease)were found by imaging examination after surgery;
3. Patients with CEA expression detected by immunohistochemistry in primary tumor andliver metastasis tumor tissues (CEA expression detected by pathology was more than 50%);
4. Life expectancy ≥6 months;
5. Performance status (PS) score 0-2, Karnofsky performance status (KPS) score above 60;
6. Patients with ctDNA MRD still positive or positive again after adjuvant chemotherapy (including preoperative neoadjuvant chemotherapy);
7. Important organ functions are sufficient, such as New York Heart Association (NYHA)heart function grade III or above, hemoglobin ≥90g/L, hypoxia; Liver function: totalbilirubin ≤1.5×ULN (total bilirubin ≤3×ULN in liver metastasis), ALT≤2.5×ULN,AST≤2.5×ULN (ALT or/and AST≤5×ULN in liver metastasis); Renal function: serumcreatinine ≤1.5×ULN and creatinine clearance rate ≥50 mL/min. The creatinine clearancerate was only calculated when serum creatinine ≤1.5×ULN. Minimum reserve of lungfunction (dyspnea no higher than grade 1 and oxygen saturation > 91% without oxygen);
8. Sufficient mononuclear cells (PBMC) can be obtained from peripheral veins withoutcontraindications;
9. Patients of childbearing age had no birth plan within 1 year after cell infusion andtook effective contraceptive measures.

Exclusion Criteria:

1. Have a history of severe central nervous system diseases;
2. Residual disease or tumor remnants can be seen in imaging, or tumor lesions cannot beresected in other tissues or organs;
3. The presence of serious non-malignant diseases, including autoimmune diseases, primaryimmunodeficiency diseases or obstructive or restrictive respiratory diseases;
4. Prior treatment with CAR-T or other gene-modified T cells;
5. Participated in other clinical studies within 30 days prior to screening or plan toparticipate in other clinical studies during the study period;
6. Patients with active Hepatitis B (HBV-DNA copy number >105copies/ml), active HepatitisC (HCV-RNA copy number >ULN), HIV infection, treponema pallidum infection at screeningtime;
7. The existence of uncontrollable systemic infectious diseases;
8. Other multiple malignant tumors in addition to colorectal cancer and its metastasis;
9. Chinese herbal medicine, systemic glucocorticoids or other immunosuppressants may berequired within 2 weeks prior to enrollment or during the trial period, which maynegatively affect lymphocyte activity or number;
10. Pregnancy and lactation;
11. The existence of severe gastroduodenal ulcer, severe ulcerative colitis and otherserious intestinal inflammation;
12. The existence of serious respiratory diseases;
13. Those who cannot provide enough white tablets for tumor pathology for next-generationsequencing (NGS) detection (at least 3 white tablets are expected);
14. The investigator judged that there were other conditions that were not suitable forthe clinical study.