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Publication : Manufacturing of primary CAR-NK cells in an automated system for the treatment of acute myeloid leukemia.

First Author  Albinger N Year  2024
Journal  Bone Marrow Transplant Volume  59
Issue  4 Pages  489-495
PubMed ID  38253870 Mgi Jnum  J:360561
Mgi Id  MGI:7834537 Doi  10.1038/s41409-023-02180-4
Citation  Albinger N, et al. (2024) Manufacturing of primary CAR-NK cells in an automated system for the treatment of acute myeloid leukemia. Bone Marrow Transplant 59(4):489-495
abstractText  Acute myeloid leukemia (AML) still constitutes a dreadful disease with limited therapeutic options. Chimeric antigen receptor (CAR)-modified T cells struggle to target AML partly due to a lack of true AML-exclusive antigens and heterogeneity of the disease. Natural killer (NK) cells possess a high intrinsic killing capacity against AML and might be well suited for the treatment of this disease. However, the generation of primary CAR-NK cells can be difficult and time consuming. Therefore, robust systems for the generation of high numbers of CAR-NK cells under GMP conditions are required. Here we report on the automated generation of high numbers of primary CD33-targeting CAR-NK cells using the CliniMACS Prodigy((R)) platform. Automated-produced CD33-CAR-NK cells showed similar phenotype and cytotoxicity compared to small-scale-produced CD33-CAR-NK cells in vitro and were able to strongly reduce leukemic burden in an OCI-AML2 NSG-SGM3 xenograft mouse model in vivo following a cross-site shipment of the cell product. This technology might be well suited for the generation of primary CAR-modified NK cells for a broad range of targets and could facilitate clinical transition.
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