Production of “off-the-shelf” allogeneic cellular CAR-immunotherapy for hematological malignancy

Chimeric antigen receptor (CAR) T-cell therapy is a new form of cancer treatment where immune cells from the patient are genetically programmed to express a CAR and transfused back to the patient thus killing the tumor cells. The therapy is effective against some hematological cancers, but challenged by high costs, treatment delay, and inferior quality of the immune cells when recovered from the often heavily pretreated patients. This has led to an interest in using allogeneic cells from healthy blood donors and to make an “off-the-shelf” product ready for immediate use. In this context NK cells have an advantage over T cells, because the latter may recognize the patient as foreign and cause so-called graft-versus-host disease. Allogeneic CAR NK cells are therefore very exciting, but many challenges remain. This project develops optimal ways of isolating, expanding, and differentiating NK cells for CAR therapy and constructs novel CAR designs to assure optimal tumor killing in patients.