Targeting chromatin complexes to reverse AML immune escape for engineered cell therapy (12)

• Subject Area: Immunology
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 318346496

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.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1292: Targeting convergent mechanisms of inefficient immunity in tumors and chronic infections
• Applicant Institution: Johannes Gutenberg-Universität Mainz
• Project Heads: Professorin Dr. Simone Fulda, until 12/2021; Professor Dr. Michael Kühn; Professorin Dr. Evelyn Ullrich