Engineering fratricide-resistant CCR4/CD7 CAR T cells with enhanced safety and persistence for T cell malignancies

Despite the remarkable success of chimeric antigen receptor (CAR)-T cell therapy in B cell malignancies, its application to T-lineage neoplasms has been hampered by antigen escape, fratricide, functional exhaustion, and severe adverse events, such as T cell aplasia, or inadvertent transduction of malignant T cells with the CAR construct (Figure 1).1 In a recent study,2 we sought to collectively address these limitations through the rational design of a bispecific CAR targeting both CD7 and CCR4 using CD7-negative (CD7N) T cells, combined with strategic functional enhancements and safety elements (Table 1).