A Study of Gene-edited GC203 TIL on the Pancreatic Ductal Adenocarcinoma

Inclusion Criteria:

1. have done the tumor resection for gene-edited GC203 TIL production and successfullyproduced；

2. Age: 18 years to 70 years;

3. Histologically diagnosed as pancreatic ductal adenocarcinoma;

4. Expected life-span more than 3 months;

5. ECOG score 0-1;

6. Test subjects have failed standard treatment regimens, and be willing to recievegene-edited GC203 TIL therapy;

7. At least 1 evaluable tumor lesion;

8. Hematology and Chemistry（within 7 days prior to enrollment）:

Absolute count of white blood cells≥2.5×10^9/L; Absolute count of neutropils≥1.5×10^9/L; Absolute count of lymphocytes ≥0.7×109/L； Platelet count≥90×10^9； hemoglobin≥90 g/L; Activated partial thromboplastin time (APTT) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days); International normalized ratio (INR) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days); Serum creatinine ≤1.5mg/dL(or ≤132.6μmol/L), or clearance rate≥50mL/min; Serum ALT/AST ≤3×ULN(subjects with liver metastasis ≤3×ULN); Totol bilirubin≤1.5×ULN; 9.Test subjects with child-bearing potential must be willing to practice approved highly effective methods of contraception at the time of informed consent, and continue within 1 year after the completion of lymphodepletion； 10.Any malignant tumor-targeting therapies, including radiotherapy, chemotherapy and biologics must cease 28 days before obtaining TILs; 12.Be able to understand and sign the informed consent document; 13.Be able to stick to follow-up visit plan and other requirements in the agreement.

Exclusion Criteria:

1. with other malignant tumors,except for the malignancies that have been cured, havebeen inactive for ≥5 years prior to study inclusion and have a very low risk ofrecurrence; Non-melanoma skin cancer or malignant lentigo with adequate treatmentand no evidence of disease recurrence; Carcinoma in situ with adequate treatment andno evidence of disease recurrence;

2. Need glucocorticoid treatment, and daily dose of Prednisone greater than 10mg(orequivalent doses of hormones) or outoimmune diseases requiring immunomodulatorytreatment;

3. Breathe indoor air in a quiet state, and the oxygen saturation of finger pulse is < 95%;

4. Human immunodeficiency virus (HIV) infection or anti-HIV antibody positive, activeHBV or HCV infection (HBsAg positive and/or anti-HCV positive), syphilis infectionor Treponema pallidum antibody positive;

5. Significant cardiovascular anomalies according to any of the following definition: New York Heart Association (NYHA) Grade III or IV congestive heart failure,clinically significant low blood pressure, uncontrollable symptomatic coronaryartery diseases, or ejection fraction less than 35%; Severe cardiac rhythm andconduction anomaly, such as ventricular arrhythmia requiring clinical intervention,second-third degree atrio-ventricular conductive block, etc.

6. Uncontrolled metabolic disorders, such as diabetes, which is known to beuncontrolled, or other non-malignant organ or systemic disease or cancer secondaryreactions, can lead to higher medical risk and/or uncertainty in the evaluation ofsurvival;

7. Patients with esophageal or gastric varices requiring immediate intervention (e.g.,ligation or sclerotherapy) or who, in the opinion of the investigator or inconsultation with a gastroenterologist or hepatologist, have evidence of portalhypertension (including splenomegalgia on imaging) or a history of varicose bleedingmust undergo endoscopic evaluation within the first 3 months of enrollment;

8. Hepatic encephalopathy, hepatorenal syndrome or Child-Pugh grade B or more severecirrhosis, liver failure;

9. Pulmonary fibrosis, interstitial lung disease (both past and present), acute lungdisease;

10. Clinically uncontrollable third space effusion, such as pleural fluid and ascitesthat could not be controlled by drainage or other means prior to enrollment;

11. Patients with known pnelmeningeal metastases; Other patients known to haveuncontrolled or untreated central nervous system metastases that are not effectivelycontrolled by treatment, except those who have been treated and whose symptoms arestable, and who discontinue glucocorticoid and anticonvulsant therapy ≥4 weeks priorto cell retransfusion;

12. Severe physical or mental diseases;

13. Have a systemic active infection requiring treatment, or have positive bloodcultures(or imaging evidence of infection);

14. Having been treated within a month or being treated now with other medicines, orother biologic therapy, chemo-or radiotherapy;

15. History of allogeneic T cell therapy;

16. Having received immunotherapy and developed irAE level greater than Level 3;

17. Previous anti-tumor treatment AE did not return to CTCAE5.0 version grade 1 or below (toxicity considered by the investigator as non-safety concerns like alopeciaexcluded);

18. Females in pregnancy or lactation;

19. History of organ transplantation, allogeneic stem cell transplantation, and renalreplacement therapy;

20. Researchers considering the test subject as having a history of other severesystemic diseases, or other reasons inappropriate for the clinical study.