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CAR-T-Zellen: Update 2019

CAR T Cells: Update 2019
: Dluczek, Sarah; Tretbar, Sandy; Fricke, Stephan; Koehl, Ulrike


Transfusionsmedizin 9 (2019), Nr.3, S.187-200
ISSN: 2191-8805
ISSN: 2191-8813
Fraunhofer IZI ()
Bibliographie; chimeric antigen receptor; CAR-T-Zelle; adoptive immunotherapy; CAR T cell production process; quality control and drug approval

Die chimäre Antigenrezeptortherapie (CAR-Therapie) entwickelte sich zu einem der vielversprechendsten immunonkologischen Therapieansätze für die Behandlung von Krebs. Aufgrund der klinischen Erfolge wurden bisher 2 CD19-spezifische CAR-T-Zell-Therapien in den USA und der EU zugelassen. Die bahnbrechenden Ergebnisse weckten sowohl in der Industrie als auch in der Forschung großes Interesse und sorgten für eine rasante Entwicklung in diesem Feld.


CAR T cells are ex vivo genetically engineered T lymphocytes carrying a tumor-specific chimeric antigen receptor (CAR) for re-targeting and killing of specific tumor cells. Up to now, CAR T cell therapy was applied for haemato-oncological diseases in the clinics. In preclinical and clinical trials, other potential target antigens especially for solid tumors are currently under investigation. However, the treatment of solid tumors with CAR T cells is still challenging since the tumors are hardly accessible for CAR T cells and other tumor infiltrating lymphocytes. The production of CAR T cells comprises autologous blood donation, followed by the isolation of T cells and the genetic modification of the T cells ex vivo. Subsequently, the modified T cells are expanded and prepared for cryoconservation and formulation as infusion. Quality control regulations ensure a reproducible CAR T cell production. Reproducibility is still challenging because of a high variability in process parameters such as parent material and non-harmonized guidelines. The European Medicines Agency (EMA) defines CAR T cells as ATMP (Advanced Therapy Medicinal Product) and is responsible for the marketing authorization. The federal state authority, however, authorizes the manufacturing of the ATPMs and the Paul-Ehrlich-Institute is responsible for the approval of the respective clinical trial. In order to improve safety and efficacy of CAR T cells, multiple strategies are currently under investigation such as integration of suicide genes, production of universal CARs (UniCAR) or inhibitory CARs (iCAR). Moreover, a promising way to treat malignant diseases is the combinatorial treatment of CAR T cells and checkpoint inhibitors, which are already tested in clinical trials.