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Primary CD33-targeting CAR-NK cells for the treatment of acute myeloid leukemia.
- Source :
- Blood Cancer Journal; Apr2022, Vol. 12 Issue 4, p1-9, 9p
- Publication Year :
- 2022
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20445385
- Volume :
- 12
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Blood Cancer Journal
- Publication Type :
- Academic Journal
- Accession number :
- 156892272
- Full Text :
- https://doi.org/10.1038/s41408-022-00660-2