Chimeric antigen receptor (CAR) T cell therapies are generating substantial excitement and have been approved for the treatment of various haematological malignancies. All approved CARs consist of an extracellular antigen-binding domain linked to an intracellular region containing a costimulatory domain and a T cell activation domain. A key question is whether the CD28-derived and 4-1BB-derived costimulatory domains used in current commercial CAR T cell products are associated with different cellular and clinical effects. Herein, Cappell and Kochenderfer provide an overview of CD28 and 4-1BB costimulatory pathways and compare the outcomes observed in preclinical and clinical studies with CARs incorporating either costimulatory domain.
- Kathryn M. Cappell
- James N. Kochenderfer
