Choose appropriate patients with advanced pancreatic cancer or other cancers, with written consent for this study;~Perform biopsy to determine the expression of Mesothelin of the tumors by western blotting or IHC;~Collect blood from the patients and isolate mononuclear cells, activate the T cells and transfect the T cells with Mesothelin targeting CAR, amplify the transfected T cells as needed, test the quality and killing activity of the CAR-T cells and then transfer them back the patients via systemic or local injections, and follow up closely to collect related results as required;~To enhance the killing capability, cotreatment the patients with PD1/PDL1/CTLA4 antibodies may be applied;~Evaluate the clinical results as needed.
The second generation of mesothelin targeted CAR-T cells that secret a fusion protein of IL21 and scfv against PD1 have been constructed and their anti-cancer function has been verified by multiple in vitro and in vivo studies. Clinical studies will be performed to test anti-cancer function of the CAR-T cells for immunotherapy of human cancer patients with Mesothelin expressions. In this phase I study, the safety, tolerance, and preliminary efficacy of the Mesothelin-CAR-T cell immunotherapy on human cancers will firstly be evaluated.