Engineered antigen-specific T-cell receptor or chimeric antigen receptor on engineered regulatory T cells (CAR-edTreg/TCR-edTreg)

Engineered antigen-specific T-cell receptors (TCR) or chimeric antigen receptors (CAR) on engineered regulatory T cells (edTregs) are synthetic signaling molecules designed to redirect the suppressive activity of regulatory T cells toward specific antigens or tissues (Honaker et al., 2020, Science Translational Medicine). The edTreg (effector-derived Treg) specifically refers to a cell population where CD4+ effector T cells are converted into a regulatory phenotype through the genetic introduction of the FOXP3 transcription factor, often combined with a CAR or TCR for specificity (PubMed: 32554709). Unlike conventional CAR-T therapies that aim to kill target cells, these engineered cells are designed to promote immune tolerance and resolve inflammation in a localized manner (Sangamo Therapeutics, 2024). Upon binding to their target antigen, these receptors trigger the Treg's natural suppressive mechanisms, including the secretion of anti-inflammatory cytokines like IL-10 and TGF-beta, the sequestration of IL-2, and the modulation of dendritic cell function (Frontiers in Immunology, 2023). This therapeutic approach is primarily being developed for autoimmune diseases such as Type 1 Diabetes and Multiple Sclerosis, as well as for preventing the rejection of transplanted organs (GentiBio, 2024; Sonoma Biotherapeutics, 2024).

Other names

Engineered regulatory T cellsedTregCAR-TregTCR-TregAntigen-specific regulatory T cellsEffector-derived regulatory T cells

Antigen-specific activation of regulatory T cells leading to localized immunosuppression through the secretion of anti-inflammatory cytokines (IL-10, TGF-beta), IL-2 sequestration, and direct suppression of effector T cells and antigen-presenting cells.