Chimeric antigen receptor (CAR) T-cell therapy has been incredibly successful in the treatment of certain B-cell leukemias and lymphomas. Dr. Michael Milone, Associate Professor of Pathology and Laboratory Medicine at the Perelman School of Medicine, is seeking to further improve on this successful platform.
Unlike natural immunoreceptors, which are multi-protein complexes, traditional CARs are generally composed of single polypeptides containing both the antigen binding and signaling functions in a single molecule. Hypothesizing that a receptor design that more closely resembles a natural immunoreceptor might provide a more robust CAR T-cell, Dr. Milone engineered T-cells to express an extracellular antigen binding domain linked to a short cytoplasmic domain derived from the killer immunoglobulin-like receptor itself.
The resultant construct, termed a “KIR-CAR”, can bind to multiple downstream signaling domains and maintains a more sustained signaling than other types of CAR-modified immune cells. Dr. Milone has founded a start-up company in partnership with Penn to further develop this patent-pending technology for multiple tumor types and is currently planning additional clinical proof-of-concept experiments.