Fas ligand (FasL) (FasL)

Fas ligand (FasL), also known as CD178 or TNFSF6, is a type II transmembrane protein belonging to the tumor necrosis factor (TNF) superfamily. In the context of islet transplantation for Type 1 diabetes, FasL is engineered (often as a streptavidin-FasL fusion protein, SA-FasL) to be displayed on the surface of transplanted beta cells to induce immune tolerance. Its primary biological function is the induction of apoptosis in cells expressing the Fas receptor (CD95), particularly activated T lymphocytes. By presenting FasL on the surface of transplanted islets, the therapy aims to eliminate alloreactive T cells that would otherwise reject the graft, while simultaneously promoting a regulatory immune environment through the recruitment of T regulatory cells. This approach, currently being developed by companies like iTolerance, represents a strategy to achieve long-term graft survival and insulin independence without the toxicities associated with systemic immunosuppressive drugs.

Other names

SA-FasLStreptavidin-Fas ligandCD178TNFSF6Tumor necrosis factor ligand superfamily member 6iTOL-100Engineered ligand on transplanted beta cells

The engineered ligand (specifically SA-FasL) is anchored to the surface of transplanted beta cells (islets) via a biotin-streptavidin linkage. It functions by binding to the Fas receptor (CD95) on infiltrating alloreactive T effector cells, triggering the extrinsic apoptotic pathway and leading to their deletion. This localized induction of apoptosis, combined with the recruitment and expansion of T regulatory cells (Tregs), establishes a state of localized immune tolerance, protecting the islet graft from rejection without the need for chronic systemic immunosuppression.