Virus-free production of CAR T-cells for the treatment of solid tumors
| Autoři | |
|---|---|
| Rok publikování | 2020 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | T-cells with chimeric antigen receptor (CAR) are powerful tool in treatment of oncologic diseases with promising clinical results, mainly in hematologic malignancies. In most of the clinical studies, reliable and efficient lentiviral transduction is used for CAR T-cells generation. However, this method has several drawbacks – e.g. the lentiviral system is expensive and requires special biohazard setting. One of the alternatives is virus-free transposon system. In our lab we investigate transposon piggyBac-based CAR T-cell generation. We focus on antigens GD2 and PSMA which are expressed abundantly on the cancer cells of neuroblastoma or melanoma and prostatic cancer cells respectively. Anti-GD2 and anti-PSMA CAR labeled with MycTag sequence are introduced into T-cells obtained either from buffy coat or peripheral blood of the donors. After 17 days we obtain almost pure population of CAR T-cells in numbers sufficient for an adult patient. Functional testing in vitro revealed that CAR T-cells are specifically activated to interferon-gamma secretion when co-cultured with relevant target cancer cell lines. Specific cytotoxic effect was observed in target cancer cell lines. Our overall aim is to transfer CAR technology into the clinical trial for solid tumor treatment. For this purpose a consortium of three institutions was established in Czech Republic – 1. Masaryk University, Brno (testing of methods in standard laboratory regime), 2. International Clinical Research Center at St. Anne's University Hospital Brno (clean-room facility in the Good Manufacturing Practice (GMP) regime), and 3. Institute of Hematology and Blood Transfusion, Praha (vector production). Close interaction with State Institute for Drug Control is maintained in order to establish the GMP-grade CAR T-cells production supported by proper pharmaceutical documentation. |
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