Background: Pancreatic cancer is an aggressive gastrointestinal cancer characterized by late diagnosis initially, prone to distant metastasis and poor prognosis. The current treatment of pancreatic cancer is very limited, resulting in its 5-year survival rate of less than 10%. It is necessary to seek new treatment methods and treatments. Chimeric antigen receptor T (CART) cell therapy has made a breakthrough in hematological malignancies. Therefore, the goal of this clinical trial is to study the safety, efficacy and pharmacokinetics of mRNA-engineered anti-Mesothelin Chimeric Antigen Receptor T-Cell (anti-MESO CAR-T cells) therapy in patients with mesothelin expression-positive, advanced pancreatic tumors that have failed at least first-line or second-line therapy. Methods: The study will adopt the "3+3" dose escalation design exploring two doses of 1×10⁹ and 3×10⁹. The administration is planned to infuse 3 times a week for 2 consecutive weeks. The subjects will receive a total dose of 1x10⁹ RNA transduced anti-MESO CAR-T cells in the first week, following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m²/day and fludarabine 30 mg/m²/day given over 3 days by intravenous infusion. If there is no obvious dose-limiting toxicity (DLT) after the first week of infusion, three times consecutive infusions of 1x10⁹ anti-MESO CAR-T cells each time is planned in the second week. Each subject needs to be observed for at least 2 weeks (14 days) after completing the last infusion. Lymphodepleting chemotherapy will not be repeated prior to additional infusions of anti-MESO CAR-T cells. Clinical trial information: 04981691.