Terapia personalizada con mRNA de neoantígenos y anticuerpo PD-1 para cáncer de páncreas postoperatorio

Fecha de inicio: 1 de abril de 2025

Inclusion Criteria: 1. Pre-Screening Phase Inclusion Criteria (for Radical Surgery and Vaccine Preparation): * Subjects meeting all of the following criteria will enter the pre-screening phase for radical surgery and vaccine preparation: * Voluntarily sign the informed consent form (ICF); * Age ≥18 years, regardless of gender; * Diagnosed with resectable pancreatic cancer as assessed per the 2024 NCCN Clinical Practice Guidelines and willing to undergo radical surgery; * ECOG Performance Status score of 0 or 1; * Ability to obtain sufficient fresh tumor tissue samples for whole-exome sequencing (WES) and transcriptome sequencing analysis; * Normal function of major organs (heart, liver, kidneys): * Liver function: Total bilirubin ≤1.5×ULN; ALT/AST ≤2.5×ULN; * Renal function: Serum creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/min (Cockcroft-Gault formula); * Cardiac function: LVEF ≥50% by echocardiography; * Contraception agreement: Fertile males and females of childbearing potential must agree to use effective contraception from signing the ICF until 6 months after the last dose of study treatment. Females of childbearing potential include premenopausal women and women ≤2 years postmenopausal; * Ability to comply with the study protocol and follow-up procedures. 2. Formal Screening Phase Inclusion Criteria (for Study Treatment Initiation): * Subjects meeting all of the following criteria will enter the formal screening phase for study treatment: * Voluntarily sign the informed consent form (ICF); * Age ≥18 years, regardless of gender; * Histologically confirmed pancreatic ductal adenocarcinoma (PDAC) post-surgery; * Completion of radical resection (R0 or R1) with no evidence of metastatic disease, malignant ascites, or pleural effusion on imaging 4-12 weeks postoperatively; * ECOG Performance Status score:Cohort A: 0 or 1;Cohort B: 0-2; * Normal function of major organs (heart, liver, kidneys): * Contraception agreement: Same as pre-screening criteria; * Ability to comply with the study protocol and follow-up procedures. Exclusion Criteria: Subjects meeting any of the following criteria will be excluded from the study: * Serum CA 19-9 level \>180 U/mL within 21 days prior to initiating standard postoperative adjuvant therapy; * History of bone marrow transplantation, allogeneic organ transplantation, or allogeneic hematopoietic stem cell transplantation; * Concurrent immunosuppressive therapy, defined as regular use of immunosuppressive agents within 4 weeks prior to screening or during the study, including but not limited to: 1. Severe asthma requiring systemic corticosteroids (≥10 mg/day prednisone equivalent); 2. Active autoimmune disease or immunodeficiency (e.g., rheumatoid arthritis, systemic lupus erythematosus); 3. History of primary immunodeficiency; 4. Exceptions: Type 1 diabetes, autoimmune hypothyroidism managed with hormone replacement, vitiligo, or psoriasis not requiring systemic therapy; * Active bacterial/fungal infections requiring systemic treatment, or active/latent tuberculosis (confirmed by interferon-gamma release assay or tuberculin skin test); * Active viral infections: 1. HIV antibody-positive; 2. Syphilis (TP antibody-positive with RPR/TRUST confirmation); 3. Active hepatitis C (HCV RNA-positive); 4. Active hepatitis B (HBsAg-positive and HBV DNA ≥2000 IU/mL); * Acute viral infections: 1. Herpesvirus infection (unless resolved with crusting \>4 weeks prior); 2. Respiratory viral infection (unless resolved \>4 weeks prior); * Uncontrolled comorbidities: 1. Symptomatic congestive heart failure (NYHA Class III/IV); 2. Unstable angina or arrhythmia requiring treatment; 3. Severe coronary/cerebrovascular disease (e.g., myocardial infarction within 6 months); 4. Other conditions deemed exclusionary by the investigator; * History of drug abuse, psychiatric disorders, or psychosocial factors impairing informed consent or protocol compliance; * History of severe hypersensitivity to vaccines, biologics, or any component of the study drug; * Pregnancy or lactation; * Other conditions judged by the investigator to preclude safe participation.