Novartis AG
TREATMENT OF CANCER USING CHIMERIC T CELL RECEPTOR PROTEINS HAVING MULTIPLE SPECIFICITIES

Abstract:

The present invention features the use of chimeric CD3 proteins to modulate T cell Receptor (TCR) signaling. Specifically, the invention is based, in part, on the discovery that multiple chimeric CD3 proteins (e.g., CD3delta, CD3gamma, and CD3 epsilon) having all or most of their extracellular domain fused to more than one antigen binding domain can activate the TCR in the presence of one or more cognate antigens. The invention is further based on the observation that the above chimeric proteins can be potentiated through the inclusion of a co-stimulatory domain in the intracellular portion of the chimeric molecule. Thus, the preferred elements of the engineered signaling complexes of the invention include more than one antigen binding domain, an extracellular domain derived from one of the above CD3 proteins, and an intracellular co-stimulatory domain.