Clinical Study of CEA-targeted CAR-T Therapy for CEA-positive Advanced Malignant Solid Tumors

Inclusion Criteria:

1. Age ≥18 years old, male or female;
2. Advanced, metastatic or recurrent malignant tumors diagnosed by histology orpathology, mainly colorectal cancer, esophageal cancer, gastric cancer, and pancreaticcancer;
3. After receiving at least second-line standard treatment and failing (diseaseprogression or intolerance, such as surgery, chemotherapy, radiotherapy, etc.) or lackof effective treatment methods;
4. Immunohistochemical staining of tumor samples within 3 months confirmed that the tumorwas CEA positive (clear membrane staining, positive rate ≥ 10%); the patient's serumCEA should exceed 10ug/L.
5. At least one assessable lesion according to RECIST 1.1 criteria;
6. ECOG score 0-2 points;
7. No serious mental disorder;
8. Unless otherwise specified, the function of the vital organs of the subject shall meetthe following conditions:
9. Blood routine: white blood cells>2.0×109/L, neutrophils>0.8×109/L, lymphocytescells>0.5×109/L, platelets>50×109/L, hemoglobin>90g/L;
10. Cardiac function: echocardiography showed cardiac ejection fraction ≥50%, and noobvious abnormality was found on electrocardiogram;
11. Renal function: serum creatinine≤2.0×ULN;
12. Liver function: ALT and AST ≤3.0×ULN (for those with liver tumor infiltration, itcan be relaxed to≤5.0×ULN);
13. Total bilirubin≤2.0×ULN;
14. Oxygen saturation > 92% in non-oxygen state.
15. Have apheresis or venous blood collection standards, and have no othercontraindications for cell collection;
16. Subjects agree to use reliable and effective contraceptive methods for contraceptionwithin 1 year after signing the informed consent form to receiving CAR-T cell infusion (excluding rhythm contraception);
17. The patients themselves or their guardians agree to participate in this clinical trialand sign the ICF, indicating that they understand the purpose and procedures of thisclinical trial and are willing to participate in the research.

Exclusion Criteria:

1. Previous CAR-T therapy or other gene-modified cell therapy；
2. CNS metastases or meningeal metastases with clinical symptoms at the time ofscreening, or there is other evidence that the patient's central nervous systemmetastases or meningeal metastases have not been controlled, and are judged by theinvestigator to be unsuitable for inclusion;
3. Participated in other clinical studies within 1 month before screening;
4. vaccinated with live attenuated vaccine within 4 weeks before screening;
5. Received the following anti-tumor treatments before screening: Received chemotherapy,targeted therapy or other experimental drug treatments within 14 days or at least 5half-lives (whichever is shorter);
6. Active infection or uncontrollable infection requiring systemic treatment;
7. Patients with intestinal obstruction, active gastrointestinal bleeding, or a historyof gastrointestinal bleeding within 3 months;
8. Except for alopecia or peripheral neuropathy, the toxicity of previous anti-tumortherapy has not improved to the baseline level or ≤ grade 1;
9. Suffering from any of the following heart diseases:
10. New York Heart Association (NYHA) stage III or IV congestive heart failure;
11. Myocardial infarction or coronary artery bypass grafting (CABG) within 6 monthsbefore enrollment;
12. Clinically significant ventricular arrhythmia, or history of syncope of unknownorigin (caused by vasovagal except those caused by neurosis or dehydration);
13. History of severe non-ischemic cardiomyopathy;
14. Patients with active autoimmune disease, or other patients requiring long-termimmunosuppressive therapy;
15. Suffering from other uncured malignant tumors in the past 3 years or at the same time,except cervical carcinoma in situ and basal cell carcinoma of the skin;
16. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive andperipheral blood hepatitis B virus (HBV) DNA titer is greater than the normal range;hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C Virus (HCV)RNA test is greater than the normal range; human immunodeficiency virus (HIV) antibodypositive; syphilis test positive;
17. Women who are pregnant or breastfeeding;
18. Other investigators deem it unsuitable to participate in the study.