Overview
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.
Description
- 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.
- 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;
- 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;
- 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;
- Evaluate the clinical results as needed.
Eligibility
Inclusion Criteria:
- patients with advanced lung tumor or other solid tumor where biopsy is obtainable
- Life expectancy >12 weeks
- Child-Pugh-Turcotte score <7
- Adequate heart,lung,liver,kidney function
- 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
- Informed consent explained to, understood by and signed by patient/ guardian. Patient/guardian given copy of informed consent. -
Exclusion Criteria:
- Had accepted gene therapy before;
- Tumor size more than 25cm;
- Severe virus infection such as HBV, HCV, HIV, et al
- Known HIV positivity
- History of lung transplantation
- Active infectious disease related to bacteria, virus,fungi,et al
- Other severe diseases that the investigators consider not appropriate;
- Pregnant or lactating women
- Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)
- Other conditions that the investigators consider not appropriate.