TY  - JOUR
A1  - Albinger, Nawid
A1  - Pfeifer, Rita
A1  - Nitsche, Marcus
A1  - Mertlitz, Sarah
A1  - Campe, Julia
A1  - Stein, Katja
A1  - Kreyenberg, Hermann
A1  - Schubert, Ralf
A1  - Quadflieg, Melissa
A1  - Schneider, Dina
A1  - Kühn, Michael W. M.
A1  - Penack, Olaf
A1  - Zhang, Congcong
A1  - Möker, Nina
A1  - Ullrich, Evelyn
T1  - Primary CD33-targeting CAR-NK cells for the treatment of acute myeloid leukemia
T2  - Blood cancer journal
N2  - Acute myeloid leukemia (AML) is a malignant disorder derived from neoplastic myeloid progenitor cells characterized by abnormal proliferation and differentiation. Although novel therapeutics have recently been introduced, AML remains a therapeutic challenge with insufficient cure rates. In the last years, immune-directed therapies such as chimeric antigen receptor (CAR)-T cells were introduced, which showed outstanding clinical activity against B-cell malignancies including acute lymphoblastic leukemia (ALL). However, the application of CAR-T cells appears to be challenging due to the enormous molecular heterogeneity of the disease and potential long-term suppression of hematopoiesis. Here we report on the generation of CD33-targeted CAR-modified natural killer (NK) cells by transduction of blood-derived primary NK cells using baboon envelope pseudotyped lentiviral vectors (BaEV-LVs). Transduced cells displayed stable CAR-expression, unimpeded proliferation, and increased cytotoxic activity against CD33-positive OCI-AML2 and primary AML cells in vitro. Furthermore, CD33-CAR-NK cells strongly reduced leukemic burden and prevented bone marrow engraftment of leukemic cells in OCI-AML2 xenograft mouse models without observable side effects.
KW  - Preclinical research
KW  - Translational research
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/69546
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-695465
SN  - 2044-5385
N1  - Open Access funding enabled and organized by Projekt DEAL.
N1  - This work was supported by the German Research Foundation (Project Number 318346496, SFB1292/2 TP12) (to EU, JC, MWMK, and NA), the Alfred and Angelika Gutermuth Foundation, the Jose Carreras Leukemia Foundation (to EU and OP), and by Miltenyi Biotec.
VL  - 12
IS  - art. 61
SP  - 1
EP  - 9
PB  - Nature Publishing Group
CY  - London [u.a.]
ER  -