Trial Information

Reinstituting Natural Killer Cell Cytotoxicity and Cytoskeletal Dynamics in Wiskott-Aldrich Syndrome With IL-2 Therapy

The Wiskott-Aldrich syndrome (WAS) is a fatal genetic disease of the immune system that
results from a mutation of the WAS protein (WASp) gene. Immune cells that carry this
mutation have a decreased ability to reorganize filamentous actin (F-actin) after
activation. As a result there are a number of defective immunologic functions, some of
which result in deficient host defense. The investigators have identified a pervasive
deficit in natural killer (NK) cell cytotoxicity in WAS patients. WAS patients suffer from
conditions that are hallmarks of NK cell deficiencies. These include severe herpesvirus
infections and B cell malignancies. Our lab and others have also found that exposure of WAS
subject NK cells to IL-2 in vitro restores NK cell function and allows for normal F-actin
reorganization. Thus, the investigators propose a proof of principal clinical trial to
treat WAS subjects with IL-2 to determine safety and efficacy of IL-2 in this population and
if NK cell function is restored ex vivo. If IL-2 can circumvent a defective WASp to restore
NK cell function, the investigators will propose a larger NIH funded efficacy trial of IL-2
in WAS. The investigators will also use the in vivo treatment of WAS subjects to forward our
mechanistic studies of how IL-2 may facilitate F-actin reorganization in the absence of WASp
function.