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

Overview

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.

Full Title of Study: “CAR-T Cell Targeting GPC3 for Immunotherapy of Hepatocellular Carcinoma: Phase I Clinical Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: August 1, 2025

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/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; 4. 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; 5. Evaluate the clinical results as needed. 6. Will also perform the similar clinical trial on lung squamous carcinoma with the GPC3 expression.

Interventions

  • 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.

Arms, Groups and Cohorts

  • Other: CAR-T cell therapy group
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • 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 Measures

  • 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.
  • Median CAR-T cell persistence
    • Time Frame: Five years
    • Median CAR-T cell persistence will be measured by quantitative rt-PCR.

Participating in This Clinical Trial

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. -

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Second Affiliated Hospital of Guangzhou Medical University
  • Collaborator
    • Hunan Zhaotai Yongren Medical Innovation Co. Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Zhenfeng Zhang, MD,PhD, Principal Investigator, Second Affiliated Hospital of Guangzhou Medical University
  • Overall Contact(s)
    • Zhenfeng Zhang, MD,PhD, 0086-020-34153532, zhangzhf@gzhmu.edu.cn

Citations Reporting on Results

Jiang Z, Jiang X, Chen S, Lai Y, Wei X, Li B, Lin S, Wang S, Wu Q, Liang Q, Liu Q, Peng M, Yu F, Weng J, Du X, Pei D, Liu P, Yao Y, Xue P, Li P. Anti-GPC3-CAR T Cells Suppress the Growth of Tumor Cells in Patient-Derived Xenografts of Hepatocellular Carcinoma. Front Immunol. 2017 Jan 11;7:690. doi: 10.3389/fimmu.2016.00690. eCollection 2016.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.