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

Second Affiliated Hospital of Guangzhou Medical University

Status and phase: Enrolling; Phase 1

Conditions: Nonsmall Cell Lung Cancer; Solid Tumor, Adult

Treatments: Biological: TCR-T cells

Study type: Interventional

Funder types: Other

Identifiers

NCT03778814

ZZTCRT-006

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

30 participants in 1 patient group

TCR-T cell therapy group

Experimental group

Description:

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

Treatment:

Biological: TCR-T cells