1. Primary CD33-targeting CAR-NK cells for the treatment of acute myeloid leukemia.
- Author
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Albinger N, Pfeifer R, Nitsche M, Mertlitz S, Campe J, Stein K, Kreyenberg H, Schubert R, Quadflieg M, Schneider D, Kühn MWM, Penack O, Zhang C, Möker N, and Ullrich E
- Subjects
- Animals, Cell Line, Tumor, Disease Models, Animal, Hematopoiesis, Humans, Immunotherapy, Adoptive, Mice, Sialic Acid Binding Ig-like Lectin 3 genetics, Killer Cells, Natural, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy
- 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., (© 2022. The Author(s).)
- Published
- 2022
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