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 Project objective

We are currently witnessing a revolution in cell therapies that are routed in decades of basic research in genetics, cell biology and immunology. A deep understanding of mammalian, and in particular immune, cells is currently being translated into highly efficient cell-based therapeutics. Technologic breakthroughs in genetic and genome engineering are further fueling the generation of customized, high precision therapies that are based on cells as “smart drugs”. For instance, reprogramming immune killer cells to recognize B cell leukemias resulted in unprecedented clinical responses in treatment-resistant and relapsed patients. However, currently only very few, highly selected patients benefit from these developments. A fundamental problem of today’s cell therapies is that transferred cells cannot be distinguished from host cells. We have developed “allele engineering”, a new technology that solves this challenge. Here, we outline how allele engineering will improve the safety and efficacy of cell therapies. We will 1) generate a non-viral, DNA-free safety/shielding switch 2) develop a radically new curative approach to acute myeloid leukemia 3) rationally design a safe allele engineering solution for human therapy and 4) use allele engineering as a curative therapy of scurfy syndrome, a lethal monogenic autoimmune disease. Allele engineering enables completely new treatment strategies and can be applied to any surface protein. Therefore, I anticipate that the results will have a major impact on the field.