CEA Targeting Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of CEA Positive Advanced 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, andpancreatic cancer;

3. After receiving at least second-line standard treatment failure (disease progressionor intolerance, such as surgery, chemotherapy, radiotherapy, etc.) or lack ofeffective treatment methods;

4. Immunohistochemical staining of tumor samples within 3 months confirmed that thetumor was CEA positive (clear membrane staining, positive rate ≥ 10%); , thepositive rate ≥ 10%), the serum CEA of the patient is required to 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 shallmeet the following conditions:

9. Blood routine: white blood cells>3.0×10^9/L, neutrophils>0.8×10^9/L,lymphocytes cells>0.5×10^9/L, platelets>75×10^9/L, hemoglobin>80g/L;

10. Cardiac function: echocardiography showed cardiac ejection fraction ≥50%, andno obvious abnormality was found on electrocardiogram;

11. Renal function: serum creatinine≤2.0×ULN;

12. Liver function: ALT and AST ≤3.0×ULN (for patients with liver tumorinfiltration, it can be relaxed to ≤5.0×ULN);

13. Total bilirubin≤3.0×ULN;

14. Oxygen saturation ≥95% 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 cellinfusion (excluding rhythm contraception);

17. The patients themselves or their guardians agree to participate in this clinicaltrial and sign the ICF, indicating that they understand the purpose and proceduresof this clinical trial and are willing to participate in the research.

Exclusion Criteria:

1. Those who have central nervous system metastasis or meningeal metastasis at the timeof screening are judged by the investigator to be unsuitable for inclusion;

2. Participated in other clinical studies within 1 month before screening;

3. vaccinated with live attenuated vaccine within 4 weeks before screening;

4. Received the following anti-tumor treatments before screening: Receivedchemotherapy, targeted therapy or other experimental drug treatments within 14 daysor at least 5 half-lives (whichever is shorter);

5. Active infection or uncontrollable infection requiring systemic treatment;

6. Patients with intestinal obstruction, active gastrointestinal bleeding, or a historyof gastrointestinal bleeding within 3 months;

7. Except for alopecia or peripheral neuropathy, the toxicity of previous anti-tumortherapy has not improved to the baseline level or ≤ grade 1;

8. Suffering from any of the following heart diseases:

9. New York Heart Association (NYHA) stage III or IV congestive heart failure;

10. Myocardial infarction or coronary artery bypass grafting (CABG) within 6 monthsbefore enrollment;

11. Clinically significant ventricular arrhythmia, or a history of unexplainedsyncope (except those caused by vasovagal or dehydration);

12. History of severe non-ischemic cardiomyopathy;

13. Patients with active autoimmune disease, or other patients requiring long-termimmunosuppressive therapy;

14. Suffering from other uncured malignant tumors in the past 3 years or at the sametime, except cervical carcinoma in situ and basal cell carcinoma of the skin;

15. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positiveand peripheral blood hepatitis B virus (HBV) DNA titer test is greater than thenormal range; hepatitis C virus (HCV) antibody positive and peripheral bloodhepatitis C Virus (HCV) RNA test is greater than the normal range; humanimmunodeficiency virus (HIV) antibody positive; syphilis test positive;

16. Women who are pregnant or breastfeeding;

17. Other investigators deem it unsuitable to participate in the research.