Tumor necrosis factor receptor superfamily member 6 (CD95) (CD95)

Tumor necrosis factor receptor superfamily member 6 (CD95) is a type I transmembrane protein that mediates the extrinsic pathway of apoptosis (UniProt: P25446). In the context of alloreactive CD8+ T cells, CD95 is a critical marker and functional regulator; these cells, which recognize foreign histocompatibility antigens, often upregulate CD95 upon activation (PubMed: 10591256). The interaction between CD95 and its ligand (FasL) is essential for activation-induced cell death (AICD), a process that normally prunes the T cell repertoire to prevent overactive immune responses (StatPearls: Fas Pathway). In diseases like Graft-versus-Host Disease (GvHD), targeting CD95 on alloreactive T cells or blocking the pathway in target organs is a therapeutic strategy to reduce tissue damage (PubMed: 25233874). Drugs like Asunercept (APG101) act as FasL decoys to prevent Fas-mediated apoptosis of healthy host cells, while other experimental approaches seek to induce apoptosis in the alloreactive T cells themselves. However, therapeutic development is challenged by the high risk of systemic hepatotoxicity, as hepatocytes are highly sensitive to Fas-mediated death (PubMed: 11071310).

Other names

FASFas receptorTNFRSF6APO-1APT1CD95 antigen

Asunercept acts as a soluble decoy receptor that binds to Fas ligand (FasL), thereby preventing its interaction with the Fas receptor (CD95) on the surface of cells and inhibiting the extrinsic apoptotic pathway (PubMed: 25233874). Conversely, Fas agonists like MegaFasL aim to trigger CD95-mediated apoptosis in target cells such as alloreactive T cells or malignant cells (PubMed: 26154451).