Immunotherapy is currently revolutionizing cancer treatment resulting in long-term effects. However, more than 80% of the patients still not benefit from current approaches. Natural Killer (NK) cell-based immunotherapies are emerging as promising cellular therapies for hematological and solid cancers. Primary NK and induced pluripotent stem cells (iPSCs)- derived NK cells have been genetically engineered to enhanced antitumor activity and are currently in clinical trials. It is possible to generate allogenic NK cells from iPSCs, however there is a risk of rejection by the recipient’s immune system, limiting their persistence. protocols to differentiate NK cells from iPSCs are complex, offering important challenges for wide adoption of NK-based therapies. We hypothesize that direct reprogramming from somatic cells represents an alternative to generate autologous NK cells for cancer immunotherapy. Here, we propose to induce NK cell fate in mouse and human fibroblasts. The work will proceed in two steps. First, we will determine the Transcription Factor (TF) combination sufficient to establish NK cell identity in mouse embryonic fibroblasts. Induced NK cells will be assessed for phenotype, transcriptome and cytotoxic function. Then, we will test the combination of TFs in human cells and evaluate the function of induced cells in vivo in mouse models. This proposal will establish a new platform to advance NK cell-based immunotherapies with the generation of autologous NK by cell reprogramming that can be combined with simultaneous genetic engineering of chimeric antigenic receptors.
Gällande start-/slutdatum2019/01/01 → …


  • Novo Nordisk Foundation