TCR-T Cell Immunotherapy of Lung Cancer and Other Solid Tumors

NCT ID: NCT03778814

Last Updated: 2024-06-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-01
• Study Completion Date: 2036-12-30

Brief Summary

Tumor organoids and TILs (and/or peripheral T cells) cultures will be established from fresh tissure of lung cancer and other solid tumors. Coculture will be utilized to screen tumor-responsive T cells which are further selected for monoclonal expansion and TCR cloning for engineered reconstitution of TCR-T cells. After verification by multiple in vitro and in vivo studies, a large number of TCR-T cells will be introduced back into the patients via vein, artery or fine needle punctured to the tumor, or combinations. In this phase I study, the safety, tolerance and preliminary efficacy of the TCR-T cell immunotherapy on human will firstly be assessed.

Detailed Description

1. Choose appropriate patients with KK-LC-1 expression in advanced lung cancer or other solid tumors and matched MHC-A11 typing, with written consent for this study; For cancer without expression of KK-LC-1, fresh tumor tissue should be obtained for RNA/DNA sequencing to computationally identify neoantigen peptides that can be captured by specifically personizedly synthesized poly-MHCI which can be further used to fish appropriate T cells from the patient.

2. Perform biopsy to obtain tissue from tumor/lymph node for organoids, TILs, DC and T cells culture, coculture to screening anti-tumor T cells, establish and select monoclonal T cells for TCR cloning;

3. Clone TCR sequence that targets KK-LC-1 or neoantigens; collect PBMCs from the blood of the patients, isolate and activate the T cells and generate the TCR-T cells;

4. Test the quality and killing activity of the TCR-T cells in vitro and then transplant back the patients via systemic (vein and/or artery) or local injections, and follow up closely to collect related clinical data as needed;

5. Evaluate the clinical results as needed.

Conditions

Nonsmall Cell Lung Cancer; Solid Tumor, Adult

Study Design

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

Study Groups

TCR-T cell therapy group

Appropriate lung cancer or other solid tumor patients who could benefit from immunotherapy will be treated with targeting TCR-T cells.

Group Type: EXPERIMENTAL

TCR-T cells

Intervention Type: BIOLOGICAL

Engineering TCR-T cells targeting lung tumor and other solid tumor will be transfused back the patients.

Interventions

TCR-T cells

Engineering TCR-T cells targeting lung tumor and other solid tumor will be transfused back the patients.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. patients with advanced lung tumor or other solid tumor where biopsy is obtainable

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 targeted TCR sequences determined by flow-cytometry and killing of tumor cells 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 lung 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

Tcell Immune (Guangzhou) Science and Technology Ltd.

UNKNOWN

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 Second Affiliated Hospital of Guangzhou Medical University

Guanzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhenfeng Zhang, MD,PhD

Role: CONTACT

zhangzhf@gzhmu.edu.cn

0086-020-34153532

Liangping Li, MD,PhD

Role: CONTACT

liangping_li@jnu.edu.cn

020-38688609

Facility Contacts

Zhenfeng Zhang, MD,PhD

Role: primary

zhangzhf@gzhmu.edu.cn

02034153532

Other Identifiers

ZZTCRT-006

Identifier Type: -

Identifier Source: org_study_id