Zusammenfassung
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.
Abstract
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.
Schlüsselwörter
chimärer Antigenrezeptor (CAR) - CAR-T-Zellen - adoptive Immuntherapie - Herstellungsprozess
- Qualitätsmanagement
Key words
Chimeric antigen receptor (CAR) - CAR T cells - adoptive immunotherapy - CAR T cell
production process - quality control and drug approval
