A revolution is taking place in the field of adoptive immunotherapy, where T cells armed with a Chimeric Antigen Receptor (CAR) are being used to fight cancerous cells. Genome engineering is at the heart of this revolution. This groundbreaking technology relies mainly on the use of engineered nucleases and makes it possible to modify the genome of the T cell to give it new properties. Specifically, the engineered T cell can be transformed into an allogeneic product, or it can resist existing cancer treatments or even overcome checkpoint inhibition. Genome engineering is regarded as one of the most important breakthroughs of recent years, and is about to revolutionize immunotherapy.