Researchers developed a novel fourth-generation CAR (CAR4) incorporating three costimulatory domains (CD28, 4-1BB, and CD27) fused to CD3ζ. Results demonstrated that these CAR-T cells not only enhanced cytotoxicity and IFN-γ production against Trop2-positive breast cancer cells but also conferred better long-term persistence and proliferative capacity. Here, CD28 is linked to breast cancer.