SYNKIT · Synthetic Natural Killer Cells for Immunotherapy
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-09-01 → 2022-08-31
- EU contribution
- €191,852
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Synthetic Natural Killer Cells for Immunotherapy
Cancer remains a leading cause of death worldwide, urging for the development of innovative therapies to help patients. Recent advances have shown that infusion of immune cells, which possess an intrinsic capacity to fight cancer such as T cells or natural killer (NK) cells, is a promising treatment option for many patients. However, infusion of cells from an unrelated donor can lead to rejection responses by the patient’s immune system, similar to how transplanted organs are often rejected. Importantly, if the infused cells are quickly destroyed by the patient’s immune system, the transferred cells cannot effectively fight the patient’s cancer, thereby limiting treatment efficacy. The overall objective of the SYNKIT action is to address this limitation of current immunotherapies by applying synthetic biology in the form of genetic engineering with the goal to reduce rejection of transferred cells. Reduced rejection will result in extended persistence of the infused cells in the patient and by this will optimise the anti-cancer function of cell therapy. Thus, successful completion of SYNKIT will pave the way for the development of next-generation immunotherapy to combat cancer more effectively.
Data: CORDIS, © European Union
Project objective
Cancer remains a leading cause of death worldwide, urging for innovative therapies. Infusion of natural killer (NK) cells, which possess an intrinsic capacity to eliminate cancer cells, is a promising treatment option for various tumours. Genetic engineering of NK cells before transfer allows to specifically tailor and modulate their anti-tumour responses. One particularly attractive strategy for broad implementation of NK cell immunotherapy in an “off-the-shelf” setting is to expand large numbers of NK cells from induced pluripotent stem cells (iPSCs). However, this approach is limited by two main bottlenecks: i) poor persistence of allogeneic iPSC-derived NK (iNK) cells due to rejection by the recipient immune system and ii) impaired functionality due to failure to achieve complete differentiation in vitro.The SYNKIT project seeks to address both of these current limitations through genetic engineering of iNK cells for increased persistence and function. Deletion of human leukocyte antigen (HLA) ""self-ligands"" allows the transferred cells to escape from host T cells. However, absence of HLA also triggers “missing-self” recognition and rejection by host NK cells. In addition, new insights from the host laboratory into the molecular mechanism underlying NK cell education have unravelled a pathway of functional disarming in NK cells that lack self-ligands, further diminishing the anti-tumour efficacy of HLA-deficient NK cells.In SYNKIT, I will use HLA-deficient iNK cells as a platform to assess how introduction of synthetic self-ligands modulates the allogenicity and functionality of iNK cells. The overall goal of SYNKIT is to identify synthetic self-ligands, which reduce recognition by the host immune system and yet prevent functional disarming of the engineered iNK cells, thereby resulting in optimised anti-tumour function.Successful completion of SYNKIT will pave the way for development of next generation immunotherapy to more effectively combat cancer.""
Original text from CORDIS.
Participants
- KAROLINSKA INSTITUTET · STOCKHOLMCoordinatorSweden
Links
Data: CORDIS, © European Union