Trial | NCT03198546  Report issue

Title

GPC3-CAR-T Cells for Immunotherapy of Cancer With GPC3 Expression
CAR-T Cell Targeting GPC3 for Immunotherapy of Hepatocellular Carcinoma: Phase I Clinical Trial

  • Phase

    Phase 1

  • Study Type

    Interventional

  • Status

    Recruiting

  • Study Participants

    30
The third/fourth generation of CAR-T cells that target GPC3 (GPC3-CART cell) and/or soluble TGFβ (GPC3/TGFβ-CART )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/TGFβ-CAR-T cells in human HCC patients with GPC3 expression. In this phase I study, the safety, tolerance, and preliminary efficacy of the GPC3/TGFβ-CAR-T cell immunotherapy on human will firstly be tested.
Choose appropriate patients with advanced hepatocellular carcinoma,with written consent for this study;
Perform biopsy to determine the expression of GPC3 of the tumor by western blotting or IHC;
Collect blood from the patients and isolate mononuclear cells, activate the T cells and transfect the T cells with GPC3/TGFβ targeting CAR (or/and scfv/cytokines-secreting), amplify the number of transfected T cells as needed, test the quality and killing activity of the GPC3/TGFβ-CART cells and then transplant back the patients via systemic or local infusions (via artery or intra-tumor), and follow up closely to collect related results as needed;
To enhance the killing capability, CD4+ T cells are genetically engineered to express TGFβ-CAR and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Tigit; CD8+T cells are constructed to express GPC3-DAP10-CAR with knockdown of PD1/HPK1;
Evaluate the clinical results as needed.
Will also perform the similar clinical trial on lung squamous carcinoma with the GPC3 expression.
Study Started
Jul 01
2017
Primary Completion
Aug 01
2022
Anticipated
Study Completion
Aug 01
2024
Anticipated
Last Update
Dec 01
2020

Biological GPC3 and/or TGFβ targeting CAR-T cells

Engineering GPC3 or/and TGFβ targeting CAR combined with/or without IL7/CCL19 and/or scfv against PD1/CTLA4/Tigit secreting vector into T cells with knockdown of PD1/HPK1, which are isolated from patients with advanced HCC, and then transfusing them back the patients.

CAR-T cell therapy group Other

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

Criteria 

Inclusion Criteria:

patients with advanced HCC,which express GPC3 protein.
Life expectancy >12 weeks
Child-Pugh-Turcotte score <7
Adequate heart,lung,liver,kidney function
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
Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. -

Exclusion Criteria:

Had accepted gene therapy before;
Tumor size more than 25cm;
Severe virus infection such as HBV,HCV,HIV,et al
Known HIV positivity
History of liver transplantation
Active infectious disease related to bacteria, virus,fungi,et al
Other severe diseases that the investigators consider not appropriate;
Pregnant or lactating women
Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)
Other conditions that the investigators consider not appropriate. -
No Results Posted