Primary CD33-targeting CAR-NK cells for the treatment of acute myeloid leukemia
- 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.
Author: | Nawid AlbingerORCiD, Rita PfeiferGND, Marcus Nitsche, Sarah MertlitzORCiDGND, Julia CampeORCiD, Katja Stein, Hermann KreyenbergORCiDGND, Ralf SchubertORCiDGND, Melissa Quadflieg, Dina SchneiderORCiD, Michael W. M. KühnORCiD, Olaf PenackORCiDGND, Congcong ZhangGND, Nina MökerGND, Evelyn UllrichORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-695465 |
DOI: | https://doi.org/10.1038/s41408-022-00660-2 |
ISSN: | 2044-5385 |
Parent Title (English): | Blood cancer journal |
Publisher: | Nature Publishing Group |
Place of publication: | London [u.a.] |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2022/04/13 |
Date of first Publication: | 2022/04/13 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2023/08/17 |
Tag: | Preclinical research; Translational research |
Volume: | 12 |
Issue: | art. 61 |
Article Number: | 61 |
Page Number: | 9 |
First Page: | 1 |
Last Page: | 9 |
Note: | Open Access funding enabled and organized by Projekt DEAL. |
Note: | 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. |
HeBIS-PPN: | 511904355 |
Institutes: | Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - CC BY - Namensnennung 4.0 International |