Dual-targeting CLDN18.2 and PD-L1 CAR-T for Patients with CLDN18.2-positive Advanced Solid Tumors

Inclusion Criteria:

1. Male or female, Age 18-75 years old;

2. Patients with pathologically/histologically confirmed diagnosis of solid tumors (such as advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinomaand pancreatic adenocarcinoma) have received at least once systemic standardtreatment and disease progressed; or refused/ cannot tolerate the subsequentialstandard treatment after the first line treatment;

3. Must have CLDN18.2-positive tumor expression ≥10% as determined by the CLDN18.2 IHCassay;

4. Estimated life expectancy > 3 months (according to investigator's judgement);

5. At least 1 measurable lesion per RECIST 1.1;

6. The Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;

7. Sufficient venous access for leukapheresis collection and no other contraindicationsto leukapheresis;

8. Patients should have reasonable CBC counts, renal and hepatic functions;

9. No other serious diseases (autoimmune diseases or any immune deficiency disease);

10. Women of childbearing age must undergo a serum pregnancy test with negative resultsbefore screening and infusion and be willing to use effective and reliable method ofcontraception for at least 12-months after T-cell infusion;

11. Men must be willing to use effective and reliable method of contraception and arenot allowed to donate sperm for at least 12-months after T-cell infusion;

12. Voluntarily participate in the research, understand and sign the informed consent.

Exclusion Criteria:

1. Pregnant or lactating women;

2. Patient with hepatitis B or C active period, HIV infection ≥ the upper limit of thenormal level;

3. Any uncontrolled active infection;

4. Patients who have clinically significant thyroid dysfunction;

5. Patients who have received prior cellular therapy such as CAR T, TCR,tumor-infiltrating lymphocytes;

6. Patients who are allergic to immunotherapy or any associated drugs, such ascytokines and the preconditioning regimen (cyclophosphamide, fludarabine);

7. Patients with untreated central nervous system (CNS) metastatic disease,leptomeningeal disease, or cord compression;

8. Patients have clinical significant cardiac conditions that researchers believe thatparticipating in this clinical trial may endanger the health of the patients;

9. Unstable pulmonary embolism, deep venous embolism or other major arterial/venousthromboembolic events occurred within 6 months before enrollment;

10. Patients with active autoimmune diseases, history of autoimmune diseases or otherdiseases in need of immunosuppressive therapy;

11. Patients with major surgery or injury less than 4 weeks prior to leukapheresis orplan to have major surgery during the research period;

12. Patients with second malignancies in addition to targeted malignancies within 5years before screening;

13. Patients with unstable/active ulcer or digestive tract bleeding;

14. Patient suffering from diseases that affect the signing of written informed consentor compliance with research procedures; or are unwilling or unable to comply withresearch requirements;

15. Patients who have a history or a tendency for digestive tract bleeding;

16. Patients who are inappropriate to participate in this research as considered by PI.