SL-9258

SL-9258 is a preclinical Agonist Redirected Checkpoint (ARC®) fusion protein developed by Shattuck Labs, currently being advanced in collaboration with Ono Pharmaceutical. The molecule is engineered as a hexameric fusion protein comprising the extracellular domain of the TIGIT receptor, an Fc linker, and the costimulatory ligand LIGHT (TNFSF14). SL-9258 functions by binding and sequestering TIGIT ligands, such as the Poliovirus receptor (PVR/CD155) and Nectin-2 (CD112), thereby blocking the inhibitory TIGIT signaling pathway on T-cells and NK-cells. Simultaneously, the LIGHT domain of the fusion protein binds to and activates the Herpesvirus entry mediator (HVEM) and Lymphotoxin beta receptor (LTbetaR), providing potent costimulatory signals. This dual mechanism is intended to overcome the immunosuppressive tumor microenvironment and stimulate a robust anti-tumor immune response in patients with refractory solid tumors.

Other names

TIGIT-Fc-LIGHT