Prevention of Graft-Versus-Host Disease via Fas Ligand Protein

Innovation
Inventors at the University of Missouri have developed a therapeutic to prevent graft-versus-host disease (GVHD) that can result from allogenic cell transplants. This treatment is achieved by labeling donor cells with FasL, which causes alloreactive T cells to self-terminate.

Background
Graft-versus-host disease occurs when allogenic T cells that are transferred from one individual (donor) to another (host), recognize host cells as foreign, and mount an immune response against the host. GVHD can manifest as an acute or chronic condition with variable severities, including the possibility of death.

FasL plays a critical role in the natural process of T-cell maturation by screening for and removing autoreactive T cells. This invention mimics the T cell screening process (known as negative selection) by attaching FasL to the donor cells via biotin-streptavidin. When a FasL-decorated T cell that is transplanted to a host binds a host antigen, it will upregulate the Fas receptor in that T cell. This upregulated Fas will then bind FasL and trigger apoptosis of the activated T cell, effectively eliminating alloreactive T cells and preventing GVHD.

Applications
- Prevention of GVHD
- Bone marrow transplant

Advantages
- Improves survivability and quality of life
- Decreases hospital stay post-transplant
- Reduces medical costs post-transplant

Patent Status
Patent pending

State of Development
Pre-clinical; Demonstrated ex vivo (mice and human cells) and in vivo (mouse models)