Issues

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the therapy of lymphoid malignancies. However, its application to other cancer types is limited due to off-cancer, on-target toxicity, as malignant cells and their normal counterparts have similar surface antigens. Here, Jambon and colleagues engineered a new type of acute myeloid leukemia (AML)-targeting CAR-T cell that minimizes the toxicity by controlling CAR receptor expression via an “IF-THEN” trigger. This new CAR-T cell expresses an AML-specific CD33-targeting “SynNotch” receptor which, when bound to CD33 on AML cells, induces the expression of the AML-killing CD123 CAR receptor. This SynNotch-controlled “IF-THEN” CAR trigger allows for more selective targeting of AML cells and decreased off-target hematopoietic toxicity. For more information, see the article by Jambon and colleagues on page 55.