Two Costimulations Are Better Than One: Role of Endogenous CD28 in 4-1BB CAR T Cells

Liberman and colleagues identify endogenous CD28 signaling as a regulator of 4-1BB chimeric antigen receptor (CAR) T-cell function by promoting metabolic fitness, proliferation, and sustained antitumor function. These findings highlight the cooperative integration of CD28 and 4-1BB signaling to harness CAR T-cell potency, persistence, and therapeutic efficacy. See related article by Lieberman et al., p. XX .