Clinical Study of Personalized mRNA Vaccine Encoding Neoantigen in Subjects With Resected Digestive System Neoplasms

Inclusion Criteria:

1. Male or female, >/= 18 years old and </= 75 years old, with the ability to understandand provide signed and witnessed informed consent, and agree and are able to complywith protocol requirements.
2. Subjects must have one of the histologically- or cytologically-confirmed advanced (locally advanced or metastatic) digestive system neoplasms listed below that can beradical resected. Subjects must be able to receive at least 4 cycles of standardadjuvant therapy according to CSCO clinical guidelines after surgery. The toxiceffects of previous anti-tumor treatments have returned to </= grade 1 defined byNCI-CTCAE v5.0 or to the level specified by the inclusion/exclusion criteria. Subjects with any of the following digestive system neoplasms: a. Cholangiocarcinoma b. Pancreatic cancer c. Hepatocellular carcinoma d. Gastriccancer e. Colorectal carcinoma
3. Expected survival >/= 6 months.
4. ECOG performance status score of 0 ~ 1.
5. Sufficient tumor tissue samples can be obtained from subjects for genetic analysis,with at least 0.5cm*0.5cm of tissue required for surgical samples.
6. Echocardiographic evaluation: left ventricular ejection fraction (LVEF) >/= 50%.
7. The organ function level must meet the following requirements: absolute neutrophilcount (ANC) >/= 1.5 × 10^9/L, platelet count (PLT) >/= 80 × 10^9/L, hemoglobin (Hb) >/= 90 g/L; serum total bilirubin (TBIL) </= 1.5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) </= 2.5 × ULN (if there is liver metastasis,TBIL </= 3 × ULN, AST, ALT </= 5 ×ULN are allowed), serum albumin >/= 28g/L, serumcreatinine </= 1.5 × BUN, Glomerular filtration rate >/= 50mL/min, prothrombin time (PT) and activated partial thromboplastin time (APTT) and international standardizedratio (INR) </= 1.5 × ULN (without anticoagulant therapy) .
8. For women of childbearing potential: having a negative serum or urine pregnancy testwithin 7 days prior to study initiation, agreement to remain abstinent or usecontraceptive measures during the treatment period.
9. For men: agreement to remain abstinent or use contraceptive measures during thetreatment period.

Exclusion Criteria:

1. Subjects with cancer requiring anti-tumor treatment within the 5 years prior toenrollment in the study (except stage I prostate cancer, cervical cancer in situ,breast cancer in situ, papillary thyroid cancer and non-melanoma skin cancer that havebeen treated).
2. Subjects who received major surgery, or had obvious traumatic injury or long-termuntreated wounds or fractures within 2 weeks prior to the first dose of iNeo-Vac-R01.
3. Subjects whose sequencing data was found that there are no new antigens available forindividualized immunotherapy after analysis.
4. Subjects who prepare to undergo or have previously received bone marrowtransplantation, allogeneic organ transplantation, or allogeneic hematopoietic stemcell transplantation. Subjects who receive other anti-tumor treatments within 2 weeksprior to the first dose of iNeo-Vac-R01, including surgical treatment, chemotherapy,radiation therapy, targeted therapy, endocrine therapy, immunotherapy, biologicaltherapy, interventional therapy, or other clinical trial related treatments.
5. Subjects who need to use immunosuppressants, or systemic or absorbable localglucocorticoids therapy to achieve immunosuppressive effects and continue to use themwithin 7 days before the first administration (excluding those with daily doses ofglucocorticoids less than 10mg of prednisone or doses of other therapeuticglucocorticoids equal to 10mg of prednisone).
6. Subjects who received other vaccines within 4 weeks before the first dose ofiNeo-Vac-R01, and are expected to receive other vaccines during treatment period ofthe study or within 60 days after the last dose of iNeo-Vac-R01.
7. Subjects who have an active infection or uncontrollable infection requiring systemictreatment, including fungi, bacteria, viruses, or other infections; subjects withactive tuberculosis;
8. Subjects with positive hepatitis B surface antigen (HBsAg) and/or positive hepatitis Bcore antibody (HBcAb) and positive hepatitis B virus DNA titer detection greater thannormal range; positive hepatitis C virus (HCV) antibody and HCV RNA detection greaterthan normal range; positive human immunodeficiency virus antibody; positive treponemapallidum-specific antibody.
9. Subjects with autoimmune diseases or immune deficiencies treated withimmunosuppressive drugs, except vitiligo, type 1 diabetes, autoimmune hypothyroidismrequiring hormone treatment and psoriasis not requiring systemic treatment; knownhistory of primary immunodeficiency.
10. Subjects with cardiocerebrovascular events: previously or currently heart valvedisease >/= grade 3, heart failure within 8 weeks before the first dose ofiNeo-Vac-R01 (New York Heart Association [NYHA] cardiac function >/= grade II,myocardial infarction, unstable angina, stroke, transient ischemic attack, cardiacsurgery (including coronary artery bypass grafting or percutaneous coronaryintervention) within 8 weeks before the first dose of iNeo-Vac-R01, concomitant severeelectrocardiogram abnormalities (such as ventricular flutter, ventricularfibrillation, multiform ventricular tachycardia, sick sinus syndrome, third degreeatrioventricular block without pacemaker treatment, QTc >/= 480ms, and otherconditions evaluated by the investigators as severe abnormalities), hypertension withpoor drug control (systolic blood pressure >/= 160mmHg and/or diastolic blood pressure >/= 100mmHg), or other cardiocerebrovascular diseases that have been evaluated by theinvestigators as unsuitable for participation in this trial.
11. Subjects with respiratory disease: previously or currently pulmonary fibrosis,interstitial lung disease, pneumoconiosis, radiation pneumonia, drug-relatedpneumonia, severe asthma, pulmonary hypertension or severe impairment of lungfunction, etc.
12. Subjects with moderate to severe ascites with clinical symptoms; uncontrolled ormoderate to equal amounts of pleural effusion and pericardial effusion.
13. Subjects with drug abuse; clinical or psychological or social factors that affectinformed consent or research implementation.
14. Subjects with a history of allergies to immunotherapy or vaccines, or other potentialimmunotherapy allergies identified by the investigators.
15. Subjects identified that it is not suitable for enrollment or may not be able tocomplete this experiment for other reasons by the investigators.
16. Vulnerable groups, including individuals with mental illness, cognitive impairment,critical patients, minors, pregnant or lactating women, etc.