Harnessing the NKG2D immune surveillance pathway using engineered T-cells for the treatment of human disease

The NKG2D receptor is a central component of immune surveillance and is expressed on natural killer (NK) cells and several T lymphocyte subsets. NKG2D functions as an activating receptor and costimulatory molecule. By recognizing stress-induced ligands, NKG2D enables immune cells to detect and eliminate virally infected, transformed and senescent cells. Recent advances in engineered T-cell therapies have harnessed this biology through the development of NKG2D-based chimeric antigen receptor (CAR) constructs. Preclinical and early clinical studies demonstrate the versatility of NKG2D-CAR T cells to treat a wide range of human disease types, thereby representing a promising frontier for broad-spectrum immunotherapy of diverse human disease types.