Mesothelin and Claudin 18.2 Dual-Target CAR-T Therapy in Advanced Pancreatic Cancer

Inclusion Criteria:

• Expected survival time ≥3 months;

• Histologically or cytologically confirmed pancreatic adenocarcinoma that is advanced (unresectable or metastatic). Patients should have received, or be intolerant of,standard first-line therapy (e.g., gemcitabine/nab-paclitaxel, FOLFIRINOX) foradvanced disease. A short course of current first-line therapy is allowed for thepurpose of bridging to manufacturing, but evidence of disease progression on orafter at least one line is required prior to infusion (for the dose-expansion phase,patients must have progressed on ≥1 prior systemic regimen).

• ECOG Performance Status: 0 or 1 (fully active or restricted in strenuous activitybut ambulatory).

• Liver and kidney function, cardiopulmonary function meet the following requirements:

• Creatinine ≤1.5×ULN; (2) Electrocardiogram showed no clinically significant abnormalbands;

• Blood oxygen saturation >91% in non-oxygen state;

• Total bilirubin ≤2×ULN; ALT and AST≤2.5 x ULN; ALT and AST abnormalities due todisease, such as liver infiltration or bile duct obstruction, were determined to beless than 5×ULN. If Gilbert syndrome is diagnosed, the total bilirubin index can berelaxed to ≤3.0×ULN and the direct bilirubin ≤1.5×ULN.

• No serious mental disorders;

• Can understand this test and has signed the informed consent.

Exclusion Criteria:

• Hepatitis B surface antigen (HBsAg) positive; Hepatitis B core antibody (HBcAb)positive and peripheral blood hepatitis B virus (HBV) DNA titer detection is notwithin the normal reference value range; Hepatitis C virus (HCV) Antibody positiveand peripheral blood hepatitis C virus (HCV) RNA positive; Human immunodeficiencyvirus (HIV) Antibody positive; Syphilis positive;

• Serious heart disease, including but not limited to unstable angina, myocardialinfarction or bypass or stent surgery (within 6 months prior to screening),congestive heart failure (NYHA classification ≥III), and severe arrhythmia;

• Systemic diseases that are deemed unstable by researchers: including but not limitedto severe liver, kidney, or metabolic diseases that require drug treatment;

• Active or uncontrollable infections (except mild genitourinary and upper respiratorytract infections) that require systemic treatment within 7 days prior toadministration;

• Pregnant or lactating women, and female subjects who plan pregnancy within 2 yearsafter cell transfusion or male subjects whose partners plan pregnancy within 2 yearsafter cell transfusion;

• Patients who received CAR-T therapy or other gene-modified cell therapy beforescreening;

• Participated in other clinical studies 1 month before screening;

• Evidence of central nervous system invasion during subject screening;

• Mental patients with depression or suicidal thoughts;

• Situations considered unsuitable for inclusion by other researchers.