Clinical Study of Personalized mRNA Vaccine Encoding Neoantigen in Patients With Advanced Digestive System Neoplasms

Inclusion Criteria: 1. Patients aged 18 - 75 with pathologically confirmed advanced Esophageal Squamous Carcinoma, Gastric Adenocarcinoma, Pancreatic Adenocarcinoma and Colorectal Adenocarcinoma. 2. Patients with advanced Esophageal Squamous Carcinoma, Gastric Adenocarcinoma, Pancreatic Adenocarcinoma and Colorectal Adenocarcinoma who have disease progression with first line chemotherapy. (1) Failure of treatment is defined as disease progression, recurrence or metastatic disease, or intolerable toxicities occurred after treatment. (2) Each line of treatment during the period of disease progression includes one or more chemotherapy drugs which are administered for not less than one cycle or even longer. Neoadjuvant/adjuvant therapy can be applied at an earlier stage of treatment. If patient has developed recurrence or metastatic disease within 24 weeks of neoadjuvant/adjuvant therapy, it is considered as one line of systemic chemotherapy. (3) Therapies that can be performed at an earlier stage are chemotherapy in conjunction with molecular targeted drugs. 3. Expected survival after first dose of study drug \> 24 weeks. 4. At least one measurable lesion (≥ 10 mm) for imaging assessment. 5. ECOG scores 0 - 1. 6. Fresh pathological tissue specimens can be obtained 7. White blood cells (WBCs) ≥ 2.5×10\^9/L * Platelets (PLT) ≥ 100×10\^9/L * Hemoglobin, Blood (Hb) ≥ 9.0 g/dL * MID ≥ 1.5×10\^9/L * Lymphocyte (LY) ≥ 0.47×10\^9/L * LY% ≥ 15% 8. Serum albumin (Alb) ≥ 30 g/L 9. Serum lipase (LPS) and serum amylase \< 1.5 ULN 10. Serum creatinine ≤ 1.5 ULN 11. Alanine aminotransferase (ALT) ≤ 2.5 ULN * Aspartate aminotransferase (AST) ≤ 2.5 ULN * If osseous metastasis or liver metastasis is developed and alkaline phosphatase • (ALP) \> 2.5 ULN, ALT and AST \< 1.5 ULN. 12. Serum total bilirubin (TBIL) ≤ 1.5 ULN 13. Prothrombin Time (PT): International Normalized Ratio (INR) \< 1.7. * PT \< (ULN + 4) s All test results should be within their normal ranges, and the patient is not receiving continuous supportive care. Exclusion Criteria: Patients with any of the following conditions are not eligible for the study. 1. Pregnant or lactating women. 2. HIV positive, HCV positive, HBV DNA copies ≥ 10\^3. 3. Uncontrolled active infection. 4. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary. 5. Allergic to immunotherapies and related drugs. 6. Untreated brain metastases or having symptoms of brain metastases. 7. Metastases to the lung: central tumor or multiple metastases. 8. Patients with heart disease for which treatment is needed or with poorly controlled hypertension. 9. Patients with unstable or active peptic ulcer or with alimentary tract hemorrhage. 10. Patients with previous organ transplantation or in preparation for organ transplantation. 11. Patients have undertaken major surgeries or have been badly injured 4 weeks before the study (blood collection), or will undertake major surgeries during the study. 12. The judgment of investigators that the patient is not able to or not willing to follow the instructions of the protocol.