engineered allogeneic regulatory T cells

Engineered allogeneic regulatory T cells (Tregs) are an adoptive cell therapy being developed as an "off-the-shelf" product to prevent graft-versus-host disease (GvHD) and organ transplant rejection. These cells are genetically modified using CRISPR-Cas9 technology to overcome the limitations of immune rejection and alloreactivity associated with allogeneic transplants. Specifically, researchers at Baylor College of Medicine have developed a triple-knockout Treg model targeting Beta-2-microglobulin (B2M) to reduce HLA class I expression and the T-cell receptor (TCRα/β) to eliminate receptor-mediated alloreactivity. Additionally, the engineering involves the knockout of Steroid Receptor Coactivator 3 (SRC-3), a transcriptional coactivator. Research indicates that while B2M and TCR deletions enhance allogeneic compatibility, the loss of SRC-3 impairs FOXP3 protein levels and the suppressive function of human Tregs, identifying SRC-3 as a critical regulator of Treg lineage stability and identity.

Other names

hypoimmunogenic human Tregsuniversal Tregstriple knockout TregsTCR+B2M+SRC-3 knockout Tregs