CD28zeta CAR-T cells

CD28zeta CAR-T cells represent a foundational class of second-generation chimeric antigen receptor (CAR) T-cell therapies. These cells are genetically modified to express a synthetic receptor that combines an extracellular antigen-binding domain (typically an scFv) with an intracellular signaling tail containing the CD28 costimulatory domain fused to the CD3ζ (zeta) activation domain. This specific architecture provides both the primary activation signal (Signal 1 via CD3ζ) and the necessary costimulatory signal (Signal 2 via CD28) upon binding to a target antigen, allowing for MHC-independent T-cell activation and proliferation. Clinically, CD28ζ CARs are known for rapid expansion and potent acute cytotoxic activity, often producing high levels of cytokines such as IL-2 and IFNγ. However, they are generally associated with shorter in vivo persistence compared to 4-1BB-based CARs and a higher incidence of cytokine release syndrome (CRS) and neurotoxicity. This platform is the basis for several FDA-approved therapies, most notably axicabtagene ciloleucel (Yescarta) and brexucabtagene autoleucel (Tecartus).

Other names

CD28-based CAR-T cellsCD-28-based CAR-T cellsCD 28-based CAR-T cellssecond-generation CD28-zeta CAR-TCD28-zeta chimeric antigen receptor T-cellsCD-28-zeta chimeric antigen receptor T-cellsCD 28-zeta chimeric antigen receptor T-cells