Clinical Study of CLDN18.2-targeting CAR T Cells in Advanced Solid Tumors With Positive CLDN18.2 Expression

Inclusion Criteria:

• Patients are eligible for screening for potential inclusion in the study:

1. The age is between 18 and 70 years old (including the boundary value), both maleand female.
2. Subjects with advanced CLDN 18.2 positive malignant solid tumors confirmed byhistology or cytology in the past (including advanced gastric cancer oresophagogastric junction adenocarcinoma, advanced pancreatic cancer, andmetastatic ovarian cancer without standard treatment).
3. All subjects are required to provide tumor tissue specimens that can be used forCLDN 18.2 analysis, which must be tumor histopathological specimens within 24months before signing the informed consent, or fresh biopsy specimens collectedwithin 6 months before cell reinfusion ; CLDN 18.2 histological staining ofbiopsy tumor tissue specimens is positive (defined as staining intensity ≥ 1+,positive rate ≥ 10%), the recommended antibody for detection is: Anti-Claudin18.2antibody.
4. Estimated life expectancy≥12 weeks.
5. At least 1 measurable lesion per RECIST version1.1;
6. ECOG performance status score of 0-1.
7. The subject has adequate organ and bone marrow function.
8. All toxic reactions caused by previous anti-tumor therapy were relieved to grade 0-1 (according to NCI CTCAE version 5.0) or to an acceptable level forinclusion/exclusion criteria.
9. Fertility status: Female patients of childbearing age or male patients whosesexual partners are females of childbearing age are willing to take medicallyapproved high-efficiency contraceptive measures such as intrauterine devices fromthe time of signing the informed consent to 6 months after the last cell infusionor condoms (women of childbearing age include premenopausal women and womenwithin 24 months of postmenopause).
10. Subjects must sign and date written informed consent.
11. Subjects must be voluntary and able to comply with predetermined treatmentregimens, laboratory tests, follow-up and other research requirements.

Exclusion Criteria:

• Subjects who meet any of the following conditions are not eligible for this study;

1. Pregnant and lactating women.
2. Known history of human immunodeficiency virus (HIV) infection; acute or chronicactive hepatitis B (HBsAg positive or HBsAb positive, and HBV-DNA positive);acute or chronic active hepatitis C (HCV antibody positive) , and HCV-RNA waspositive). Syphilis antibody positive; EB virus DNA quantification >500 copies (or according to the positive standard detected by each research center);cytomegalovirus (CMV) infection (IgM positive).
3. Serious infection in active stage or poorly controlled clinically.
4. There is currently a heart disease requiring treatment or hypertension that ispoorly controlled by the investigator (defined as systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure > 90 mmHg after standardizedantihypertensive drug treatment).
5. Within 6 months before cell reinfusion, any of the following cardiac clinicalsymptoms or diseases: left ventricular ejection fraction (LVEF) < 50%; previoushistory of coronary heart disease, myocardial infarction, severe heart failureand severe arrhythmia.
6. Evidence of major coagulation disorder or other significant bleeding risk:including but not limited to receiving conventional anticoagulation therapy (suchas warfarin or heparin). Patients require long-term antiplatelet therapy (aspirin, dose >300mg/day; clopidogrel, dose >75mg/day); dipyridamole,ticlopidine or cilostazol, etc.
7. Subjects requiring systemic therapy with corticosteroids or otherimmunosuppressive drugs during the treatment period.
8. Blood oxygen saturation ≤95% before treatment (refers to pulse oxygen detection).
9. Diffuse lung metastases.
10. Past history of interstitial lung disease, drug-induced interstitial lungdisease, radiation pneumonitis, and symptomatic interstitial lung disease oractive pneumonia found on chest CT scan within 4 weeks before the first studydrug treatment.
11. Uncontrollable pleural effusion, pericardial effusion and ascites effusionexisted before enrollment.
12. Poorly controlled diabetes (glycated hemoglobin HbA1c ≥ 8%).
13. Received systemic steroids equivalent to >15mg/day prednisone within 2 weeksbefore apheresis, except inhaled steroids.
14. The subject has developed new arrhythmias, including but not limited touncontrolled arrhythmias, hypotension requiring vasopressors, bacterial, fungalor viral infections requiring intravenous antibiotics prior to preconditioning .Subjects using the trial antibiotic to prevent infection were at the discretionof the investigator to continue participating in the trial.
15. Known past or current hepatic encephalopathy requiring treatment; patients withcurrent or history of central nervous system disease; central nervous systemmetastases or meningeal metastases with clinical symptoms, or other evidence ofcentral nervous system metastases or Meningeal metastases have not yet beencontrolled, and were judged by the investigator to be unsuitable for enrollment.
16. Patients with previous or concomitant malignancies, with the followingexceptions: Adequately treated basal cell or squamous cell carcinoma, curedcervical or breast carcinoma in situ, primary malignancy that has been completelyresected and complete remission for ≥5 years.
17. Received other CAR-T therapy and TCR-T therapy in the past.
18. Received the following treatments or drugs before cell reinfusion: within 28 daysbefore cell reinfusion, received chemotherapy, biological therapy, endocrinetherapy, immunotherapy and other anti-tumor treatments (treatments that met therequirements of the plan before reinfusion, such as bridging therapy) Exceptfor), or any unmarketed experimental drug treatment; received traditional Chinesemedicine treatment with anti-tumor indications within 2 weeks before cellreinfusion.
19. Subjects who have received other gene therapy in the past.
20. Subjects with severe mental disorders.
21. Participated in other clinical studies within the past 1 month.
22. The investigator assesses that the subject is unable or unwilling to comply withthe requirements of the research protocol.
23. Subjects withdrew from the study for various reasons and could not participate inthe study again.