Chimeric Antigen Receptor T Cells Targeting Glypican-3

Inclusion Criteria:

1. Aged 18 to 70 years, male or female;
2. Patients with advanced hepatocellular carcinoma (HCC) diagnosed by histopathology or cytology who are not suitable for surgery or local treatment (including ablation, intervention, and radiotherapy), have developed progressive disease or intolerability after standard systemic therapies (including but not limited to systemic chemotherapy, molecular targeted therapy) and have no effective treatment at the time of enrollment;
3. According to RECIST 1.1, patients have at least one evaluable target lesion, defined as: the longest diameter of non-lymph node lesion ≥ 10 mm, or the shortest diameter of lymph node lesion ≥ 15 mm); hepatic lesions require arterial phase contrast enhancement;
4. In tumor tissue samples GPC3 is detected positive by immunohistochemistry (IHC);
5. According to Barcelona Clinic Liver Cancer staging(BCLC), the patients are classified into Grade C or Grade B unsuitable for local treatment/progressive disease after local treatment;
6. Expected survival is > 12 weeks;
7. Cirrhosis status Child-Pugh score: Grade A;
8. Eastern Cooperative Oncology Group(ECOG) Performance Status score: 0 to 1 point;
9. Without active hepatitis B and/or Hepatitis C;
10. Have venous accesses for pheresis;
11. Acceptable routine blood test showing no contraindication to the lymphodepletion pretreatment;
12. Adequate liver, renal, cardiovascular, respiratory function;
13. Subjects of childbearing age must undergo a serum pregnancy test within 14 days before the initiation of the study and the result must be negative. In addition, they should be willing to use a reliable method of contraception during the trial (within 24 months (M24) after cell infusion); male subjects whose spouses are women of childbearing age should undergo sterilization surgery or agree to use a reliable method of contraception during the trial;
14. Understand and sign informed consent.

Exclusion Criteria:

1. Pregnant or breast-feeding women;
2. HCV-RNA(Hepatitis C Virus RNA ), HIV antibodies or Syphilis Serological tests are positive;
3. HBV（Hepatitis B） and HCV(Hepatitis C virus ) infection exist simultaneously;
4. Any uncontrollable active infection
5. Patients who had received systemic steroids or other immunosuppressive agents
6. Previous or present hepatic encephalopathy;
7. Current clinically significant ascites;
8. ≥50% of the liver is replaced by tumor or portal vein main tumor thrombus, or tumor thrombus invasion of mesenteric vein / inferior vena cava;
9. Metastases to the central nervous system and clinically significant central nervous system diseases;
10. Patients with existing heart disease in need of treatment or hypertension that be poorly controlled
11. Patients with known active autoimmune diseases which require to be treated with immunosuppressive agents including biological agents;
12. Patients with a history of organ transplantation or waiting for organ transplantation (including liver transplantation);
13. Patients with local treatments such as surgical treatment, interventional therapy, radiotherapy, ablation or systemic chemotherapy were performed for the studied disease within 2 weeks prior to apheresis;Or received immunotherapy (PD-1/ PD-L1 monoclonal antibody, see Section 15) or any Chinese herbal or proprietary medicine for the control of liver cancer within 1 week prior to apheresis;Or received sorafenib, regofenib, ramvastinib and other tyrosine kinase inhibitor targeted drugs within 1 week prior to apheresis;Targeted therapy with anti-angiogenic monoclonal antibodies such as bevacizumab or its analogue 4 weeks prior to apheresis;
14. Patiens with previous treatment with targeted GPC3, TCR-T or CAR-T;
15. Patients who previously received anti-PD-1/ PD-L1 monoclonal antibody therapy within 4 weeks prior to apheresis;
16. Patients who had uncured malignant tumors in the past 5 years or at the same time, excluding in situ cervical cancer and skin basal cell carcinoma;
17. Other serious illnesses that may limit subjects to participate in the trial (such as poorly controlled diabetes mellitus, severe cardiac insufficiency , myocardial infarction or unstable arrhythmia or unstable angina pectoris within the last 6 months, lung embolism, chronic obstructive pulmonary diseases, interstitial pulmonary diseases,gastric ulcer, a history of gastrointestinal bleeding or a clear tendency to gastrointestinal bleeding;
18. According to the investigators' evaluation, patients are unable or unwilling to comply with the requirements of the study protocol.