Exploratory Clinical Study of Claudin18.2-Targeted Activated DC and CAR-T Therapy in Advanced Pancreatic Cancer.

Inclusion criteria

• Age ≥ 18 years, upper limit ≤ 80 years, gender not limited;
• Participants must have a histologically or cytologically confirmed diagnosis of advanced pancreatic cancer, with at least one measurable lesion meeting RECIST v1.1 criteria (i.e., a target lesion with a longest diameter ≥10 mm on spiral CT scan, or a lymph node with a short axis ≥15 mm).
• Tumor tissue positive for Claudin 18.2 by immunohistochemical detection (expression intensity ≥ 2+; expression range ≥ 50%);
• Meeting the indications for PBMC collection and having no other contraindications for cell collection;
• Failure of standard second-line treatment or lack of a standard treatment regimen; or signing a refusal to undergo chemotherapy.
• ECOG score: 0-1;
• Life expectancy: ≥ 3 months;
• Toxic reactions from previous chemotherapy and other anti-tumor treatments must be resolved through a washout period (except for residual hair loss), ensuring that all functional parameters meet the inclusion criteria;
• Sufficient organ function, including:

• Sufficient immune function, i.e., absolute lymphocyte count (ALC) ≥ 0.5 × 10⁹/L, absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L, monocyte count ≥ 0.1 × 10⁹/L.
• Sufficient hematopoietic function, i.e., platelet count ≥ 75 × 10⁹/L, hemoglobin ≥ 90 g/L. Patients must not have received blood transfusions or treatments such as granulocyte colony-stimulating factor, thrombopoietin, or erythropoietin within 14 days prior to the complete blood count examination. c) Sufficient liver function, i.e., total bilirubin (TBIL) < 2 × upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 × ULN.

d) Sufficient kidney function, i.e., creatinine (Cr) ≤ 1.5 × ULN. e) Sufficient coagulation function, i.e., prothrombin time (PT) or activated partial thromboplastin time (APTT) < 1.5 × ULN, and international normalized ratio (INR) < 1.5.

• Individuals of fertility must be willing to use contraception;
• Sufficient understanding and willingness to sign an informed consent form;
• Willingness to comply with visit schedules, medication plans, laboratory tests, and other trial procedures.

Exclusion criteria

• Emergency oncological conditions requiring immediate treatment, such as malignant pericardial effusion or tamponade, superior vena cava obstruction syndrome, spinal cord compression, etc.
• Significant cardiovascular disease, such as:

• • A confirmed cardiovascular event within the past 6 months, such as myocardial infarction, angina pectoris, heart failure, severe arrhythmia, or previous angioplasty, stent implantation, or coronary artery bypass grafting;
• • Clinically significant QT interval prolongation (QTcF > 470ms for women or QTcF > 450ms for men).
• Clinically significant bleeding tendency or coagulation disorders, such as hemophilia;
• HIV infection, syphilis infection, hepatitis B infection, or hepatitis C infection.
• History of involuntary custody due to mental illness or other mental illness deemed unsuitable for treatment by the treating physician;
• Accompanied by other autoimmune diseases, or long-term use of immunosuppressants or steroids;
• Poor patient compliance as assessed by the investigator;
• Previous treatment with any target CAR-T within 3 months prior to this CAR-T treatment;
• Uncontrollable active bacterial or fungal infections;
• Other conditions deemed necessary to be ruled out by the physician.