Caruso S, De Angelis B, Del Bufalo F, et al. Safe and Effective Off-the-Shelf Immunotherapy Based on CAR.CD123-NK Cells for the Treatment of Acute Myeloid Leukaemia. Journal of Hematology & Oncology. 2022; 15 (doi: 10.1186/s13045-022-01376-3).
Researchers have demonstrated the viability of an adoptive immunotherapy strategy for acute myeloid leukemia (AML) that employs natural killer (NK) cells engineered to express anti-CD123+chimeric antigen receptor (CAR). The CD123 antigen is highly present in the leukemia cells of children with AML, but T cell-based immunotherapy is persistently undermined by on-target off-tumor toxicity. In their work, which included two humanized models of AML in immune-deficient mice, investigators observed that CAR.CD123-NK cells boasted a superior safety profile compared with CAR T cells in terms of both hematopoietic and endothelial on-target off-tumor toxicity. They observed that mice infused with CAR.CD123 NK cells survived the experiment, with no associated toxicity, while all of the mice infused with CAR.CD123 T cells developed toxicity against primary human bone marrow cells and perished within five days. The investigational approach also produced an anti-leukemia effect in vitro on par with that achieved by CAR T-cell therapy. The study authors envision using CAR.CD123-NK cells not only for refractory and resistant AML but also possibly for the treatment of other cancers that are difficult to target with the usual T effector cells.
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