Dual-specific targeted NK cells post allogeneic stem cell transplantation to improve anticancer effect against myeloid leukemia stem cells (C10*)

• Subject Area: Hematology, Oncology
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 24899777

The new project C10 will modify NK cells to specifically recognize acute myeloid leukemia (AML) stem cells. One advantage of NK cells is that they can enhance a GvL effect without causing GvHD. Due to the limited life span of NK cells, their potential for off-target toxicity is low and they do not need to be equipped with additional suicide genes. C10 will develop a chimeric antigen-receptor (CAR) system to specifically activate NK cells. The use of a CAR should overcome tumor escape mechanisms, especially in AML-stem cells. To increase the efficiency in targeting those small initiator populations, C10 will use bispecific CARs simultaneously targeting CD44v6 and CD123. Due to the experience in clinical trials, the group will further enhance the immune function of modified NK cells by transient expression of IL-2 by the modified NK-cells.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 738: Optimisation of Conventional and Innovative Transplants
• Applicant Institution: Medizinische Hochschule Hannover
• Project Head: Professorin Dr. Ulrike Köhl