Application of mRNA Immunotherapy Technology in Hepatitis B Virus-related Refractory Hepatocellular Carcinoma

Inclusion Criteria:

1. Male or female patients: ≥ 18 years old; ≤ 70 years old;
2. Patients with HBV-positive advanced hepatocellular carcinoma after failure of second-line standard therapy (including PD-1 inhibitor therapy, chemotherapy, and anti-vascular targeted drugs);
3. HBsAg positive, regardless of whether the peripheral blood is positive for HBV DNA.
4. ECOG physical fitness score: 0\~1 points;
5. Estimated survival ≥ 3 months;
6. The main organs have good function, that is, the relevant examination indicators within random 14 days meet the following requirements:

   1. Blood routine examination: hemoglobin ≥ 80 g/L (no blood transfusion within 14 days); Neutrophil count\> 1.5×109/L; Platelet count≥ 80×109/L;
   2. Biochemical examination: total bilirubin ≤ 1.5× ULN (upper limit of normal); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5×ULN; If liver metastases are present, ALT or AST ≤ 5×ULN; Endogenous creatinine clearance

      ≥ 60 ml/min (Cockcroft-Gault formula);
   3. Cardiac Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥50%.
7. Sign the informed consent form;
8. Good compliance, family members agree to cooperate with survival follow-up.

Exclusion Criteria:

1. Participated in clinical trials of other drugs within 4 weeks;
2. The patient has a history of other tumors, unless it is cervical cancer in situ, treated cutaneous squamous cell carcinoma or bladder epithelial tumor or other malignant tumors that has received radical treatment (at least 5 years before enrollment)
3. Patients with uncontrolled cardiac clinical symptoms or diseases, such as heart failure above NYHA grade 2, unstable angina, myocardial infarction within 1 year, and clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
4. For female subjects: pregnant or lactating women.
5. The patient has active tuberculosis, bacterial or fungal infection (≥ grade 2 of NCI-CTC, 3rd edition); There is HIV infection with active HBV infection, HCV infection.
6. Those who have a history of psychotropic drug abuse and have mental disorders that cannot be remitted;
7. The subject has any active autoimmune disease or has a history of autoimmune disease (such as, but not limited to uveitis, enteritis, pituitary inflammation, nephritis, hyperthyroidism, hypothyroidism; Participants with vitiligo or who had complete remission of asthma in childhood and did not require any intervention in adulthood could be included; Participants in asthma requiring medical intervention with bronchodilators omitted).
8. According to the judgment of the investigator, there are concomitant diseases that seriously endanger the safety of patients or affect the completion of the patient's research.