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

NCT ID: NCT03198546

Last Updated: 2024-06-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-01
• Study Completion Date: 2036-08-01

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.

Conditions

Hepatocellular Carcinoma; Immunotherapy; CAR; GPC3 Gene Inactivation; T Cell; Squamous Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: OTHER

GPC3 and/or TGFβ targeting CAR-T cells

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Eligibility 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. -

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hunan Zhaotai Yongren Medical Innovation Co. Ltd.

OTHER

Sponsor Role: collaborator

Guangdong Zhaotai InVivo Biomedicine Co. Ltd.

OTHER

Sponsor Role: collaborator

First Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital of Guangzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhenfeng Zhang, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital of Guangzhou Medical University

Locations

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status: RECRUITING

The Second Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhenfeng Zhang, MD,PhD

Role: CONTACT

zhangzhf@gzhmu.edu.cn

0086-020-34153532

Peng Li, PhD

Role: CONTACT

lipeng@invivobio.com.cn

+86 20 32015300

Facility Contacts

Xianhong Xiang, MD,PHD

Role: primary

Yonghui Huang, MD,PHD

Role: backup

Zhenfeng Zhang, MD,PhD

Role: primary

zhangzhf@gzhmu.edu.cn

+86-020-34153532

Deji Chen, MD,PhD

Role: backup

chendeji2003@163.com

+86-020-34153532

References

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.

Reference Type: RESULT

PMID: 28123387 (View on PubMed)

Pang N, Shi J, Qin L, Chen A, Tang Y, Yang H, Huang Y, Wu Q, Li X, He B, Li T, Liang B, Zhang J, Cao B, Liu M, Feng Y, Ye X, Chen X, Wang L, Tian Y, Li H, Li J, Hu H, He J, Hu Y, Zhi C, Tang Z, Gong Y, Xu F, Xu L, Fan W, Zhao M, Chen D, Lian H, Yang L, Li P, Zhang Z. IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin. J Hematol Oncol. 2021 Jul 29;14(1):118. doi: 10.1186/s13045-021-01128-9.

Reference Type: DERIVED

PMID: 34325726 (View on PubMed)

Other Identifiers

ZZCART-003

Identifier Type: -

Identifier Source: org_study_id