TS-057778 —
A novel monoclonal antibody (PIIO-1) targeting t
he ligand-free form of GARP, t
he non-signaling docking receptor for TGFβ. PIIO-1 distrupts transforming growth factor-β (TGF-β) signalling in t
he tumor microenvironment, primarily on T regulatory cells, consequently augmenting anti-tumor immunity and overcoming ICB resistance . Unlike market competitors, ABBV-151 and DS-1055a which bind t
he TGF-β1/GARP complex, PIIO-1 prevents activation of all 3 TGF-β isoforms, avoiding isoform compensation and avoiding t
he potential on-target, adverse effects of binding t
he TGF-β1/GARP complex found on platelets.
Although immune checkpoint blockade (ICB) has emerged as a promising cancer immunotherapy, a majority of tumors fail to respond to ICB. A potential mechanism driving this failed response is the activation of TGF-β1 in the tumor microenvironment (TME), which drives immune dysfunction by induci…