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

Phase 1

Recruiting

• Conditions: T Cell; Hepatocellular Carcinoma; Squamous Cell Lung Cancer; Immunotherapy; GPC3 Gene Inactivation; CAR
• Interventions: Biological: GPC3 and/or TGFβ targeting CAR-T cells

• Registration Number: NCT03198546
• Lead Sponsor: Second Affiliated Hospital of Guangzhou Medical University

Brief 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.

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.

Study Timeline

• Study First Submitted: 2017-06-21
• Study First Submitted QC: 2017-06-23
• Study First Posted: 2017-06-26
• Study Start: 2017-07-01
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-22
• Last Update Posted: 2024-06-25
• Primary Completion: 2029-08-01
• Study Completion: 2036-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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. -

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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. -

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR-T cell therapy group	GPC3 and/or TGFβ targeting CAR-T cells	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.

Primary Outcome Measures

Name	Time	Method
Number of Patients with Dose Limiting Toxicity	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

Name	Time	Method
Percent of Patients with best response as either complete remission or partial remission.	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	Five years	Median CAR-T cell persistence will be measured by quantitative rt-PCR.

Trial Locations

Locations (2)

The Second Affiliated Hospital of Guangzhou Medical University; 🇨🇳 Guangzhou, Guangdong, China

The First Affiliated Hospital of Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China