GPC3-T2-CAR-T Cells for Immunotherapy of Cancer With GPC3 Expression

Brief Summary:

The third generation of CAR-T cells that target GPC3 (GPC3-T2-CAR-T cell)have been constructed and their anti-HCC function has been verified by multiple in vitro and in vivo studies.Clinical studies will be performed to test the anti-cancer function by the GPC3-T2-CAR-T cells in human HCC patients with GPC3 expression.In this phase I study, the safety,tolerance, and preliminary efficacy of the GPC3-T2-CAR-T cell immunotherapy on human will firstly be tested.

*Hepatocellular CarcinomaImmunotherapy* CARGPC3 Gene Inactivation T Cell *Squamous Cell Lung Cancer

Biological: GPC3 targeting CAR-T cells

Detailed Description:

1.     Choose appropriate patients with advanced hepatocellular carcinoma,with written consent for this study;

2.     Perform biopsy to determine the expression of GPC3 of the tumor by western blotting or IHC;

3.     Collect blood from the patients and isolate mononuclear cells,activate the T cells and transfect the T cells with GPC3 targeting CAR, amplify the number of transfected T cells as needed,test the quality and killing activity of the GPC3-T2-CAR-T cells and then transplant back the patients via systemic or local injections, and follow up closely to collect related results as needed;

4.     Evaluate the clinical results as needed.

5.     Will also perform the similar clinical trial on lung squamous carcinoma with GPC3 expression

Arms and Interventions

Arm

CAR-T cell therapy group

Appropriate patients who could benefit from the GPC3 targeting CAR-T cell therapy against HCC are chosen to be the CAR-T cell therapy group.

Interventions

Biological: GPC3 targeting CAR-T cells

Engineering GPC3 targeting CAR into T cells isolated from patients with advanced HCC, and then transfusing them back the patients

Primary Outcome Measures :

1.     Number of Patients with Dose Limiting Toxicity [ Time Frame: three months ]

A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the GPC3-T2-CAR T cells, which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5.

Secondary Outcome Measures :

1.     Percent of Patients with best response as either complete remission or partial remission. [ Time Frame: three months ]

Response rates will be estimated as the percent of patients whose best response is either complete remission or partial remission by combining the data from the patients. To compare with historical data, a 95% confidence interval will be calculated for the response rate.

2.     Median CAR-T cell persistence [ Time Frame: Five years ]

Median CAR-T cell persistence will be measured by quantitative rt-PCR.

Criteria

Inclusion Criteria:

1.     patients with advanced HCC,which express GPC3 protein.

2.     Life expectancy >12 weeks

3.     Child-Pugh-Turcotte score <7

4.     Adequate heart,lung,liver,kidney function

5.     Available autologous transduced T cells with greater than or equal to 20% expression of GPC3 CAR determined by flow-cytometry and killing of GPC3-positive targets greater than or equal to 20% in cytotoxicity assay

6.     Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. -

Exclusion Criteria:

1.     Had accepted gene therapy before;

2.     Tumor size more than 25cm;

3.     Severe virus infection such as HBV,HCV,HIV,et al

4.     Known HIV positivity

5.     History of liver transplantation

6.     Active infectious disease related to bacteria, virus,fungi,et al

7.     Other severe diseases that the investigators consider not appropriate;

8.     Pregnant or lactating women

9.     Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)

10. Other conditions that the investigators consider not appropriate