The potential of engineered TCRαβ T cells as potent mediators of leukemic clearance has been demonstrated in clinical trials, and authorised therapies are being deployed against B cell malignancies in particular. While most applications have relied on harvest and manipulation of autologous lymphocytes, the emerging application of genome editing technology has demonstrated that allogeneic TCRαβ cells can be engineered to overcome Human Leukocyte Antigen (HLA) barriers and provides a route to more cost effective and widely accessible ‘off-the-shelf’ therapies. Genome editing also offers the prospect of addressing other hurdles such as shared-antigen expression and has been applied to direct site-specific transgene integration, for improved transcriptional regulation and function.