GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR-CAR-T Cells Against Cancers

NCT ID: NCT03198052

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 generation of CAR-T cells that target GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR have been constructed respectively and their anti-cancer function has been verified by multiple in vitro and in vivo studies.Clinical studies will be performed to test the anti-cancer function of the these individual or combination of the CAR-T cells for immunotherapy of human cancer patients with GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR expressions. In this phase I study, the safety, tolerance, and preliminary efficacy of the GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR

-CAR-T cell immunotherapy on human cancers will firstly be tested.

Detailed Description

1. Choose appropriate patients with advanced lung or other cancers,with written consent for this study;

2. Perform biopsy to determine the expression of HER2, Mesothelin, Lewis-Y, PSCA, MUC1, GPC3, AXL, EGFR, Claudin18.2, or B7-H3 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, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR targeting CAR, amplify the transfected T cells as needed, test the quality and killing activity of the CAR-T cells and then transfer them back the patients via systemic or local injections, 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/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR

-DAP10-CAR with knockdown of PD1/HPK1;

5. Other cancers with these cell surface antigen expressions are also recruited if needed;

6. Evaluate the clinical results as needed.

Conditions

Lung Cancer; Cancer; Immunotherapy; CAR-T Cell

Study Design

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

Study Groups

CAR-T cell therapy group

Patients will receive 3 or more cycles of the CAR-T cells treatment via systemic or regional injection, from 1x10e6/kg-10x10e6/kg weight.

Group Type: EXPERIMENTAL

CAR-T cells targeting GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR

Intervention Type: BIOLOGICAL

CAR-T cells injection: (1-10×10e6/kg CAR-T for each treatment; 3 or more cycles.

Interventions

CAR-T cells targeting GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR

CAR-T cells injection: (1-10×10e6/kg CAR-T for each treatment; 3 or more cycles.

Intervention Type: BIOLOGICAL

Other Intervention Names

Administration of CAR-T cells through vein or interventional technique.

Eligibility Criteria

Inclusion Criteria

1. Patients with advanced cancer that expresses GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR protein; 2. Life expectancy >12 weeks; 3. Adequate heart,lung,liver,kidney function; 4. Available autologous transduced T cells with greater than or equal to 20% expression ofGPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR-CAR determined by flow-cytometry and killing of GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR-positive targets greater than or equal to 20% in cytotoxicity assay; 5. 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. Severe virus infection such as HBV,HCV,HIV,et al;

3. Known HIV positivity;

4. Active infectious disease related to bacteria, virus,fungi,et al;

5. Other severe diseases that the investigators consider not appropriate;

6. Pregnant or lactating women;

7. Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day);

8. 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

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

Deji Chen, MD,PhD

Role: backup

chendeji2003@163.com

+86-020-34153532

References

Wei X, Lai Y, Li J, Qin L, Xu Y, Zhao R, Li B, Lin S, Wang S, Wu Q, Liang Q, Peng M, Yu F, Li Y, Zhang X, Wu Y, Liu P, Pei D, Yao Y, Li P. PSCA and MUC1 in non-small-cell lung cancer as targets of chimeric antigen receptor T cells. Oncoimmunology. 2017 Feb 6;6(3):e1284722. doi: 10.1080/2162402X.2017.1284722. eCollection 2017.

Reference Type: RESULT

PMID: 28405515 (View on PubMed)

Other Identifiers

ZZCART-002

Identifier Type: -

Identifier Source: org_study_id