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1. (WO2018144535) TREATMENT OF CANCER USING CHIMERIC T CELL RECEPTOR PROTEINS HAVING MULTIPLE SPECIFICITIES

Pub. No.:    WO/2018/144535    International Application No.:    PCT/US2018/016139
Publication Date: Fri Aug 10 01:59:59 CEST 2018 International Filing Date: Thu Feb 01 00:59:59 CET 2018
IPC: C07K 14/725
C07K 16/30
Applicants: NOVARTIS AG
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Inventors: ENGELS, Boris
GRANDA, Brian, Walter
GUIMARAES, Carla
LOEW, Andreas
RAMONES, Melissa
Title: 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.