Application of mRNA Immunotherapy Technology in Epstein-Barr Virus-related Refractory Malignant Tumors

Inclusion Criteria:

1. Male or female patients: ≥18 years old and ≤70 years old.
2. Patients with EBV-positive advanced malignant tumors after failure of second-line standard therapy.
3. ECOG physical condition score: 0-1 point.
4. Expected survival period ≥ 3 months.
5. The main organs are in good function, that is, the relevant inspection indicators within 14 days before randomization meet the following requirements:

   1. Blood routine examination: hemoglobin ≥ 90g/L and neutrophil count \> 1.5×109/L and platelet count ≥ 80×109/L.
   2. Biochemical examination: total bilirubin≤1.5×ULN (upper limit of normal value), blood alanine aminotransferase (ALT) or blood aspartate aminotransferase (AST)≤2.5×ULN. if there is liver metastasis, ALT or AST≤5×ULN. Endogenous creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula).
   3. Cardiac Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ 50%.
6. Sign the written informed consent

   1. Subjects must sign and date the EC-approved written informed consent in accordance with the guidelines of the competent authority and the research institution. Informed consent must be signed prior to any protocol-related procedures that are not part of the subject's routine medical care.
   2. Subjects must be willing and able to comply with the scheduled visits, treatment plans, laboratory tests, and other requirements of the study.

Exclusion Criteria:

Patients who meet any of the following criteria cannot be enrolled:

1. Participated in other drug clinical trials within 4 weeks;
2. The patient has a history of other tumors, unless it is cervical cancer in situ, treated skin squamous cell carcinoma or bladder epithelial tumor or other malignant tumors that have received radical treatment (at least 5 years before enrollment);
3. There are clinical symptoms or diseases of the heart that cannot be well controlled, such as: heart failure above NYHA grade 2, unstable angina, myocardial infarction within 1 year, clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention of patients.
4. For female subjects: pregnant or lactating women.
5. Patients have active pulmonary tuberculosis, bacterial or fungal infection (≥2 grades of NCI-CTCAE 5.0); HIV infection, active HBV infection, HCV infection.
6. Those who have a history of psychotropic drug abuse and cannot quit or have mental disorders;
7. The subject has any active autoimmune disease or has a history of autoimmune disease (such as the following, but not limited to: uveitis, enteritis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; the subject suffers from Subjects with vitiligo or asthma that had been completely remitted in childhood and who did not require any intervention in adulthood could be included; subjects with asthma requiring medical intervention with bronchodilators could not be included).
8. Any abnormalities or permanent body art (such as tattoos) at the inoculation site that, in the opinion of the investigator, would prevent observation of local reactions at the inoculation site.
9. Patients who have been vaccinated with mRNA drugs.
10. Have participated in clinical trials involving lipid nanoparticles (one of the components of the vaccine in this study).
11. There are contraindications for intramuscular injection
12. History of drug abuse or known medical, psychological or social conditions, such as history of alcohol or drug abuse.
13. Known allergy, hypersensitivity or intolerance to the research vaccine (including any excipients). There is a history of severe allergy to any drug, food, or vaccination, such as anaphylactic shock, allergic laryngeal edema, allergic dyspnea, allergic purpura, thrombocytopenic purpura, local allergic necrotic reaction (Arthus reaction), etc.
14. From the screening period to 12 months after the full injection of the drug, the female subject has a pregnancy plan or the partner of a male subject has a pregnancy plan.
15. According to the investigator's judgment, there are concomitant diseases that seriously endanger the patient's safety or affect the patient's completion of the study.