Centre hospitalier universitaire Sainte-Justine

Published purpose

Natural killer (NK) cells are lymphocytes that demonstrate cytotoxic activity towards cancer cells and are associated with good prognosis when present in solid tumors. In the past, NK cells have been used in adoptive cell transfer to treat various cancer with relative success. More recently, NK cells, modified with chimeric antigen receptor (CAR-NK cells), are being explored as potential off-the-shelf therapy and these have shown better efficacy and lower toxicity than equivalent CAR-T cells in pre-clinical animal models. However, mechanisms preventing the full cytotoxic anti-tumor activity of NK cells remain understudied. Hence, this project seeks to use whole-genome CRISPR screens in both NK and solid tumor cells to identify genes that, when inhibited, potentiate the cytotoxic activity of NK cells towards cancer cells. In turn, these genes will be therapeutically targeted or genetically modified in future iPSC-derived NK and CAR-NK cells to improve outcome in cancer patients.