Targeting chromatin complexes to reverse AML immune escape for engineered cell therapy.
The menin-MLL chromatin complex is a dependency and therapeutic opportunity in acute myeloid leukemia (AML). We found that pharmacological inhibition of the menin-MLL protein interaction (Men-i) induces expression of surface immune targets on AML cells including the C-type lectin-like receptor CLEC12A that is not expressed on hematopoietic stem cells. Here, we will engineer CLEC12A-directed CAR-NK cells to be combined with Men-i against AML. Detailed assessment of the combined treatment in AML models and characterization of the Men-i effects CAR-NK cell function may give insight into chromatin-based mechanisms of immune escape and provide a potentially more efficient immuno-epigenetic treatment against AML.
(Bilder: Goethe-Universität Frankfurt am Main/Universitätsmedizin Mainz)