Dual-Target CAR-NK Cells Targeting Mesothelin (MSLN) and MUC1 in Advanced Pancreatic Ductal Adenocarcinoma (DUAL-NK-PDAC)

Inclusion Criteria:

• Age 18 to 75 years at the time of consent.
• Histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC).
• Unresectable locally advanced or metastatic disease with progression after at least 1 prior standard systemic therapy regimen, or intolerance/ineligibility for standard therapy.
• At least 1 measurable lesion per RECIST v1.1.
• Tumor antigen expression by central IHC (archival or fresh biopsy): • Arm A eligibility: MSLN positive and/or MUC1 positive. • Arm B eligibility: CLDN18.2 positive and/or MUC1 positive. (Example threshold: IHC 2+ or 3+ staining in >=50% of tumor cells, or H-score above protocol-defined cutoff.)
• ECOG performance status 0-1.
• Adequate organ function (example): ANC >= 1.0 x 10^9/L; platelets >= 75 x 10^9/L; hemoglobin >= 8 g/dL; AST/ALT <= 3x ULN (<= 5x ULN with liver metastases); total bilirubin <= 1.5x ULN; creatinine clearance >= 50 mL/min.
• Life expectancy >= 12 weeks.
• Negative pregnancy test for individuals of childbearing potential; agreement to use effective contraception during study participation and for a protocol-defined follow-up period.
• Ability to understand and willingness to sign written informed consent.

Exclusion Criteria:

• Active or untreated CNS metastases or carcinomatous meningitis.
• Clinically significant uncontrolled infection (including uncontrolled bacterial, fungal, or viral infection).
• Known active hepatitis B or hepatitis C with detectable viral load; known uncontrolled HIV infection.
• Prior allogeneic hematopoietic stem cell transplant or solid organ transplant.
• Prior gene-modified cellular therapy (e.g., CAR-T/CAR-NK) within 6 months or prior therapy targeting the same antigen(s) Ongoing requirement for systemic immunosuppressive therapy (e.g., chronic corticosteroids above physiologic replacement).
• Clinically significant cardiovascular disease (e.g., recent myocardial infarction, uncontrolled arrhythmia, or NYHA class III/IV heart failure) within a protocol-defined period.
• Active autoimmune disease requiring systemic treatment in the past 2 years (replacement therapy allowed).
• Pregnant or breastfeeding.
• Any medical, psychiatric, or social condition that, in the investigator's opinion, would interfere with safe participation or interpretation of results.