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

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

This is an open-label, single-arm clinical study designed to evaluate the safety and preliminary efficacy of Claudin18.2 Targeted Activated DC combined with CAR-T therapy in patients with Advanced Pancreatic Cancer.

This combination therapy activates dendritic cells (DCs) to precisely target the tumor site, reshaping the tumor immune microenvironment, breaking down the immunosuppressive barrier, and allowing CAR-T cells to penetrate deeper into the tumor more efficiently, precisely and persistently killing cancer cells.

Inclusion Criteria:

1. Age ≥ 18 years, upper limit ≤ 80 years, gender not limited;

2. 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).

3. Tumor tissue positive for Claudin 18.2 by immunohistochemical detection (expression intensity ≥ 2+; expression range ≥ 50%);

4. Meeting the indications for PBMC collection and having no other contraindications for cell collection;

5. Failure of standard second-line treatment or lack of a standard treatment regimen; or signing a refusal to undergo chemotherapy.

6. ECOG score: 0-1;

7. Life expectancy: ≥ 3 months;

8. 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;

9. Sufficient organ function, including:

   1. 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.
   2. 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.

10. Individuals of fertility must be willing to use contraception;

11. Sufficient understanding and willingness to sign an informed consent form;

12. Willingness to comply with visit schedules, medication plans, laboratory tests, and other trial procedures.

Exclusion Criteria:

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

2. Significant cardiovascular disease, such as:

   1. • 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;
   2. • Clinically significant QT interval prolongation (QTcF > 470ms for women or QTcF > 450ms for men).

3. Clinically significant bleeding tendency or coagulation disorders, such as hemophilia;

4. HIV infection, syphilis infection, hepatitis B infection, or hepatitis C infection.

5. History of involuntary custody due to mental illness or other mental illness deemed unsuitable for treatment by the treating physician;

6. Accompanied by other autoimmune diseases, or long-term use of immunosuppressants or steroids;

7. Poor patient compliance as assessed by the investigator;

8. Previous treatment with any target CAR-T within 3 months prior to this CAR-T treatment;

9. Uncontrollable active bacterial or fungal infections;

10. Other conditions deemed necessary to be ruled out by the physician.