RecruitingPhase 1NCT03198546

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


Sponsor

Second Affiliated Hospital of Guangzhou Medical University

Enrollment

30 participants

Start Date

Jul 1, 2017

Study Type

INTERVENTIONAL

Conditions

Summary

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.


Eligibility

Min Age: 18 YearsMax Age: 75 Years

Inclusion Criteria6

  • 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 Criteria10

  • 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. -

Interventions

BIOLOGICALGPC3 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.


Locations(2)

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

The Second Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

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NCT03198546


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