Refine
Document Type
- Article (5)
Language
- English (5)
Has Fulltext
- yes (5)
Is part of the Bibliography
- no (5) (remove)
Keywords
- Antifungal agents (1)
- Aspergillosis (1)
- Clinical effectiveness (1)
- Hematologic malignancies (1)
- High-risk patient (1)
- Influenza (1)
- Invasive candidiasis (1)
- Invasive fungal infection (1)
- Mycoses (1)
- Neutropenia (1)
Institute
- Medizin (5)
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.