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1. (WO2018204520) MESOTHELIN-TARGETED TRAIL TRIMER

Pub. No.:    WO/2018/204520    International Application No.:    PCT/US2018/030700
Publication Date: Fri Nov 09 00:59:59 CET 2018 International Filing Date: Thu May 03 01:59:59 CEST 2018
IPC: C07K 16/30
A61K 39/00
C07K 14/705
Applicants: WASHINGTON UNIVERSITY
SPITZER, Dirk
HAWKINS, William
Inventors: SPITZER, Dirk
HAWKINS, William
Title: MESOTHELIN-TARGETED TRAIL TRIMER
Abstract:
The present disclosure provides constructs that comprise (a) a TNF-related apoptosis-inducing ligand (TRAIL) trimer comprising three consecutive extracellular TRAIL domains fused together in a head-to-tail configuration; (b) an epitope binding agent, and (c) optionally one or more additional components, wherein the epitope binding agent competitively inhibits binding of P4-TR3 or HN1-TR3 to cell surface human mesothelin. Constructs of the present disclosure induce apoptosis in cells expressing human mesothelin and a death receptor (DR4 or DR5) on the cell's surface.