Overview
Tumor infiltration lymphocytes (TILs) have been harvested from advanced cancer patients and constructed to knockout PD1 gene and express scFvs against both PD1 and CTALA4 and CARs against various antigens, followed by transfusion into the patients. The safety, tolerance, and preliminary clinical efficacy of the TILs will be evaluated.
Description
- Choose appropriate patients with advanced lung or other cancers, with written consent for this study;
- Perform biopsy or collect cancerous effusion in thorax or abdomen to obtain TILs by standard protocol;
- Grow TILs and engineered the tumor-effective TILs with CRISPRA-CAS9 technique to knockdown PD1 and electronic-transfection strategy to express scFvs that target PD1 and CTLA4; amplify the engineered T cells as needed, test the quality and killing activity of the TILs and then transfuse them back the patients via systemic or local injections via standard protocol, and follow up closely to collect related parameters as needed;
- To enhance the killing capability, tumor-noneffective TILs have also been genetically engineered to express various CARs targeting HER2/Mesothelin/Lewis-Y/PSCA/MUC1/ GPC3/AXL/EGFR/Claudin18.2/B7-H3/ROR1/GD2/AXL/Claudin6-DAP10 with knockdown of PD1/HPK1 as appropriate;
- Evaluate the clinical results as needed.
Eligibility
Inclusion Criteria:
- Patients with advanced cancers that failed to current available therapies;
- Life expectancy >12 weeks;
- Adequate heart, lung, liver, kidney functions;
- Available for tumor biopsy or cancerous effusions;
- 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;
- Severe virus infection such as HBV, HCV, HIV, et al; Known HIV positivity;
- 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.