Acute myeloid leukemia (AML) is a common and serious form of leukemia in adults, especially among elderly or frail individuals who cannot undergo an allogeneic stem cell transplantation. The current challenge is to develop new, effective therapies with fewer side effects. One promising approach is immunotherapy with genetically modified immune cells, known as CAR-T cells, which have proven successful in the treatment of lymphatic blood cancers. However, the use of CAR-T cells for AML faces challenges, as proliferative CAR-T cells could potentially mediate harmful effects on healthy cells.
Therefore, the DKTK NoviCARAZA research team will investigate the use of natural killer (NK) cells for CAR therapy as they may offer advantages, especially when targeting antigens present on both cancer and healthy cells. In addition, therapy with the anti-leukemic drug 5′-azacitidine (AZA) on AML cells has been found to upregulate specific surface proteins that make them more susceptible to immune cell therapy. NoviCARAZA aims to combine AZA with genetically modified CAR-NK cells that specifically target the AZA-induced leukemia-associated antigen. In addition, this approach involves novel non-viral technologies to transfer the CAR gene in combination with CRISPR modifications of the NK cells. The long-term goal is to translate the development of this innovative combination therapy into early clinical trials for the treatment of elderly AML patients.