Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Greinix, HT.
Role of CAR-T cell therapy in B-cell acute lymphoblastic leukemia.
MEMO-MAG EUR MED ONC. 2020; 13(1): 36-42.
Doi: 10.1007/s12254-019-00541-8
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- Führende Autor*innen der Med Uni Graz
- Greinix Hildegard
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- Abstract:
- Chimeric antigen receptor (CAR) T cells are genetically engineered cells containing fusion proteins combining an extracellular epitope-specific binding domain, a transmembrane and signaling domains of the T cell receptor. The CD19-CAR T cell product tisagenlecleucel has been approved by the US Food and Drug Administration and the European Medicines Agency for therapy of children and young adults under 25 years with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) due to a high overall response rate of 81% at 3 months after therapy. The rates of event-free and overall survival were 50 and 76% at 12 months. Despite the high initial response rate with CD19-CAR-T cells in B-ALL, relapses occur in a significant fraction of patients. Current strategies to improve CAR-T cell efficacy focus on improved persistence of CAR-T cells in vivo, use of multispecific CARs to overcome immune escape and new CAR designs. The approved CAR-T cell products are from autologous T cells generated on a custom-made basis with an inherent risk of production failure. For large scale clinical applications, universal CAR-T cells serving as "off-the-shelf" agents would be of advantage. During recent years CAR-T cells have been frequently used for bridging to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed/refractory B-ALL since we currently are not able to distinguish those CAR-T cell induced CRs that will persist without further therapy from those that are likely to be short-lived. CAR-T cells are clearly of benefit for treatment following relapse after allogeneic HSCT. Future improvements in CAR-T cell constructs may allow longer term remissions without additional HSCT.
- Find related publications in this database (Keywords)
- Chimeric antigen receptor T cells
- CAR-T cells
- Acute lymphoblastic leukemia
- B-ALL
- Allogeneic hematopoietic stem cell transplantation