Personalized Tumor Vaccines and Pabolizumab in Patients With Advanced Pancreatic Cancer

Inclusion Criteria: Subjects voluntarily signed written informed consent files,Able to comply with the study protocol, in the investigator's judgment Subjects must be >/= 18 years of age at time of informed consent, regardless of gender Subjects with locally advanced, recurrent or metastatic solid tumors confirmed by histology or cytology within the past 6 months, who have failed standard treatment or are currently not suitable for standard treatment No copy number variations (CNVs) or loss of heterozygosity (Loss-of heterozygosity, LOH) were found in HLA-related genes and chromosomal regions by gene sequencing Advanced or metastatic lesions confirmed by immunohistochemistry, and cryopreserved tissues/cells, enough for WES and RNAseq sequencing, and predicted by bioinformatics analysis, at least one antigen effectively presented by self-HLA was found , such as KRAS or TP53 mutations and correspondingly presented HLA types Life expectancy ≥ 4 months Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale Have adequate organand bone marrow function,No use of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), red blood cell transfusion and platelet transfusion within 14 days before the examination. Fertile eligible patients (male and female) must agree to use reliable contraceptive methods (hormone or barrier method or abstinence) during the trial and at least 90 days after the last dose. female patients of childbearing age before the first dose A blood pregnancy test within 7 days must be negative. Subjects need to undergo virological examination: those without CMV and EBV, HIV, HBV, HCV, and syphilis infection (only in the baseline period) Exclusion Criteria: Has had chemotherapy, hormone therapy, traditional Chinese medicine, or biological cancer(for mitomycin and nitrosoureas within 6 weeks from the first dose of the drug in this study)， prior to the first dose of study therapytherapy within 4 weeks ,Or within 5 half-lives of immunotherapy, molecular targeted therapy Subjects have undergone major surgical procedures other than the diagnosis or biopsy of the current tumor within 4 weeks before the first dose of mRNA-0217/S001, or are expected to undergo major surgery during the study period Subjects have received allogeneic hematopoietic stem cell transplantation or organ transplantation in the past, or those who plan to receive organ transplantation during this study Subjects have previously received other tumor vaccines or cell therapy Brain metastases with clinical symptoms, spinal cord compression, cancerous meningitis, or other evidence that the brain and spinal cord metastases have not been controlled, and the researchers judged that they are not suitable for enrollment Other malignant tumors known to be progressing or requiring active treatment in the past 2 years (except for non-melanoma skin cancer, superficial bladder cancer, and carcinoma in situ of the cervix that have been cured by surgical curative treatment) History of interstitial lung disease (ILD), pulmonary fibrosis Have a history of serious cardiovascular and cerebrovascular diseases, including but not limited to a) severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrioventricular block corrected QTc interval male > 450 milliseconds, female > 470 milliseconds, b) Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other cardiovascular and cerebrovascular events of grade 3 or above occurred within 6 months before the first administration, c) New York Heart Association (NYHA) ≥ III heart failure or left ventricular ejection fraction (LVEF) < 50%. Other serious and/or uncontrollable diseases, which may affect the subject's participation in this study, include but not limited to a) a history of severe drug allergy, or is known to be allergic to any tumor vaccine and pembrolizumab formulation components or has had severe allergic reactions to other monoclonal antibodies in the past, b) A history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, c) Evidence of severe or uncontrolled liver or kidney disease, d) Uncontrolled high blood pressure, diabetes, etc., e) Patients with active ulcers, gastrointestinal bleeding, f) Serious infection requiring intravenous antibiotics or hospitalization or uncontrolled active infection within 4 weeks before the first dose, g) have an active syphilis infection. Participate in other clinical trials within 4 weeks before the first dose (except for screening failure) Those who are currently receiving systemic steroids (except those who have recently or currently used inhaled steroids) Pregnant and lactating women Imaging (CT or MRI) shows that the tumor invades large blood vessels and has a tendency to hemorrhage Have clinically significant thyroid dysfunction, and the investigator judges that they are not suitable for enrollment Active pneumonia found in chest CT scan during the screening period Uncontrolled pleural effusion, pericardial effusion, or ascites that needs repeated drainage Subjects who have adverse reactions of the previous anti-tumor therapy have not recovered to NCI-CTCAE 5.0 grade evaluation ≤ grade 1 (except for hair loss) HBsAg positive and peripheral blood HBV DNA detection value is higher than the upper limit of normal, and/or HCV Ab positive and HCV RNA detection value is higher than the upper limit of normal Researchers believe that there are other reasons that are not suitable for participating in clinical trials