Single-arm, open-label, interventional study evaluating adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TIL) infusion followed by IL-2 after a non-myeloablative(NMA) lymphodepletion preparative regimen for the treatment of patients with advanced liver cancer.

This is an adoptive cell transfer therapy that utilizes an autologous TIL manufacturing process for the treatment of patients with advanced liver cancer. The cell transfer therapy used in this study involves patients receiving a non-myeloablative lymphodepletion preparative regimen, followed by i.v. infusion of autologous tumor-infiltrating lymphocytes followed by the administration of a regimen of IL-2.

Inclusion Criteria:

• The subjects must be informed of the study before the test and voluntarily sign a written informed consent.
• Age of the patients was between 18~70 years
• Eligible patients have histologically proven advanced liver cancer
• Eastern Cooperative Oncology Group (ECOG) performance status was 0-1
• Metastatic lesions are confirmed by PET-CT, CT, MR and/or intraoperative exploration (more than 3, at least one accessible metastasis to procure for TILs)
• Patients have at least one separate additional measurable tumour lesion according to RECIST version 1.1 standard.
• The disease has progressed after at least two previous lines of standard treatment and there is no effective treatment option available
• Adequate normal organ and marrow function were present, including absolute neutrophil count ≥ 1×10^9/L, leukocyte count ≥ 3×10^9/L, platelet count ≥ 75×10^9/L, hemoglobin ≥ 80 g/L, AST and ALT ≤ 2× of upper limit of normal, Serum creatinine ≤ 1.5× upper normal limits, Serum total bilirubin ≤ 1.5× upper normal limits
• Female subjects of childbearing age must have a negative urine or serum HCG test within 7 days before cell reinfusion
• Provide at least one gram of fresh tumor tissue and 10ml of peripheral blood for whole exome sequencing and TIL isolation and culture.
• Expected survival was at least 3 months
• Child-Push liver function score grade is A within seven days before the cell reinfusion.

Exclusion Criteria:

• With previous or concurrent other active cancer (except carcinoma in situ that has been cured without onset within 5 years, or those that can be cured by adequate treatment)
• Patients with metastasis to Central Nervous System or brain
• Have received organ transplantation in the past
• Received major liver surgery within 4 weeks before the first administration (except liver metastases biopsy).
• Received local treatment of the liver or other parts within 4 weeks before the first administration (transcatheter arterial chemoembolization [TACE], transcatheter arterial embolization [TAE], hepatic artery infusion [HAI], radiotherapy, radioembolization or ablation). Subjects are not eligible to participate in the study if the above-mentioned treatment is carried out between the last dose of sorafenib or oxaliplatin-containing regimen and the first study administration.
• After CT angiography examination, there is severe arterial embolism or hepatic artery vascular variation.
• APTT or PT >= 5 UNL, or with bleeding evidence in two months or bleeding history in prior to the clinical study, no matter how serious it is
• Active inflammation within 7 days after systemic antibiotics treatment
• Subjects who have undergone major surgery or severe trauma such as laparotomy, thoracotomy, and laparoscopic organ removal within 4 weeks before enrollment.
• Active coronary artery disease, serious or unstable angina pectoris, or newly diagnosed angina pectoris or myocardial infarction within 12 months prior to the clinical study
• Thrombosis or embolism event within 12 months prior to the clinical study, such as cerebrovascular accident ( including TIA) or pulmonary embolism
• Congestive heart failure of NYHA >= Class II
• Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis (hepatitis B, defined as HBV-DNA ≥ 500 IU/ml C Hepatitis, defined as HCV-RNA higher than the detection limit of the analytical method) or co-infection with hepatitis B and hepatitis C.
• Presence of any active, known or suspected autoimmune disease. Subjects in a stable state who do not require systemic immunosuppressive therapy are allowed, such as: type 1 diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, and skin diseases that do not require systemic therapy (e.g., vitiligo, psoriasis disease and hair loss).
• Any interstitial lung disease, noninfectious causes of lung inflammation, or uncontrolled systemic disease (e.g. diabetes, pulmonary fibrosis, or acute pneumonia)
• Any adverse event of CTCAE (Ver 5.0) grade 2 or higher induced by previous treatment, except anemia, hair loss, and skin pigmentation
• Pregnant or lactating women or those who are positive in pregnancy test before 1st injection
• The investigator believes that the subject has any clinical or laboratory abnormalities or compliance problems and is not suitable for participating in this clinical study.
• With serious psychological or mental abnormalities
• Joined other clinical trials in four weeks prior to this study
• Patients who have a history of hypersensitivity to cyclophosphamide and fludarabine.
• Other researchers think that they are not suitable for enrollment.