Chimeric antigen receptor (CAR) T-cells are widely being investigated against malignancies, and allogeneic 'universal donor' CAR-T cells offer the possibility of widened access to pre-manufactured, off-the-shelf therapies. Different genome-editing platforms have been used to address human leukocyte antigen (HLA) barriers to generate universal CAR-T cell therapy and early applications have been reported in children and adults against B cell malignancies. Recently developed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based systems and related technologies offer the prospect of enhanced cellular immunotherapies for a wider range of hematological malignancies.