CD28 co-stimulatory domain (CD28)

The CD28 co-stimulatory domain is a critical intracellular component of second-generation Chimeric Antigen Receptors (CARs) used in engineered T cell therapies. Derived from the naturally occurring CD28 receptor, this domain provides the necessary secondary signal for robust T cell activation following the primary signal from the CD3-zeta chain (Esensten et al., 2016, Immunity, PMID: 27096318). When the extracellular portion of the CAR binds to its target antigen, the CD28 domain triggers downstream signaling pathways, most notably the PI3K/Akt pathway, which promotes rapid T cell proliferation, enhanced cytokine production (such as IL-2 and IFN-gamma), and increased glycolytic metabolism (Kawalekar et al., 2016, Immunity, PMID: 26885861). In clinical applications, CAR-T cells incorporating the CD28 domain, such as Axicabtagene ciloleucel, are primarily used to treat various B-cell malignancies (FDA, 2017, Yescarta Prescribing Information). While CD28-based CARs are known for their rapid and potent effector response, they are also associated with a higher risk of toxicities like Cytokine Release Syndrome (CRS) and may exhibit shorter persistence compared to CARs using the 4-1BB co-stimulatory domain (Salter et al., 2018, Blood, PMID: 30245430).

Other names

CD28 signaling domainCD28 endodomainCD28 intracellular domainCD28 costimulatory domainCD28 cytoplasmic domain

Provides co-stimulatory signaling via the PI3K/Akt pathway to enhance T cell activation, proliferation, and effector function upon antigen binding by the chimeric antigen receptor.