Clinical trial NCT03778814: TCR-T Cell Immunotherapy of Lung Cancer and Other Solid Tumors
Official title: TCR-T Cells Targeting Cancer Cells for Immunotherapy of Lung Cancer and Other Solid Tumors: Phase I Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Nonsmall Cell Lung Cancer
Solid Tumor, Adult
Keywords: Lung Cancer; Solid Tumor
Immunotherapy
TCR-T Cell Therapy
Lead sponsor: Second Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
Collaborators: name: Tcell Immune (Guangzhou) Science and Technology Ltd.
First posted: 2018-12-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Patients with Dose Limiting Toxicity
timeFrame: three months
Secondary outcomes:
measure: Percent of Patients with best response as either complete remission or partial remission
timeFrame: three months
Other outcomes:
measure: Median TCR-T cell persistence
timeFrame: Five years
Locations:
city: Guanzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: Second Affiliated Hospital of Guangzhou Medical University
name: Zhenfeng Zhang, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: