This is a multicenter, open-label, paired control study to evaluate the safety and clinical efficacy of allogeneic NK cells combined with targeted drug in the treatment for advanced HCC.

Since killer cell immunoglobulin-like receptor (KIR) mismatch can inhibit the negative regulatory signal of autologous major histocompatibility complex (MHC) molecules and ensure sufficient NK cell activation, allogeneic NK cells therapy, as a potential therapeutic option for tumor, has achieved good results in patients with acute myeloid leukemia. In this study, investigators evaluate the safety and efficacy of allogeneic NK cells in the treatment of advanced HCC. 200 patients from three hospitals will be enrolled in this study and followed up for 1 year. Peripheral blood mononuclear cells (PBMCs) were isolated from patient-related donor and cultured in vitro for 15 days and infused to the patient in two consecutive days. Clinical data and laboratory data were collected and analyzed, including survival, impact indicators, hematology, biochemical indicators, and immunological indicators to evaluate the safety and efficacy of the treatment.

Inclusion Criteria:

• According to the 2010 edition of the diagnostic criteria for primary liver cancer BCLC, the patient was diagnosed as advanced hepatocellular carcinoma by pathology and imaging (BCLC C phase);

• Child-Pugh A/B (5-9), Eastern Cooperative Oncology Group (ECOG) PS score less than 2 points;

• Laboratory criteria:

  1. Liver function: Child A/B, ALT < 200 U/L, AST < 200 U/L, Tbil <51μmol/L
  2. Renal function: Creatinine clearance ≥ 60ml/minute
  3. Hematologic function: PLT ≥40×10'9/L, WBC ≥2×10'9/L, HGB>80 g/L
  4. Cardiac function: No abnormality in cardiac enzyme and ECG

• Survival expectation is greater than 6 months;

• Patients with active hepatitis B or C were treated with the appropriate NA or DAA medication, and all patients enrolled in the group were treated with targeted drugs.

• The patient has a donor who meets the donor enrollment criteria and all patients and donors sign the Informed Consent Form;

Exclusion Criteria:

• Women who are pregnant or breast-feeding.
• Co-infected with hepatitis A, hepatitis E, AIDS or other infectious diseases.
• Patients with serious complications such as acute infection and gastrointestinal bleeding within 30 days.
• Patients with other serious systemic and psychiatric diseases.
• Exposure to any cell therapy such as, but not limited to CIK, DC, CTL , PD-1 and stem cells therapy 6 months prior to study drug administration.
• Other conditions that researchers believe may increase the risk of subjects or lead to affected study results, such as the presence of mental illness in subjects.