TIGIT

Class

Fc-silent anti-TIGIT monoclonal antibody (domvanalimab)

Pathway

Immune checkpoint inhibitor; blocks inhibitory TIGIT signaling, allowing PVR to bind the activating receptor DNAM-1 on immune cells

TIGIT is an inhibitory receptor found on the surface of certain immune cells, particularly T cells and natural killer (NK) cells, that are responsible for recognizing and destroying abnormal cells such as tumor cells. TIGIT binds a ligand called PVR, which is often overexpressed on tumor cells, and this binding dampens immune cell activity. A separate receptor, DNAM-1, competes with TIGIT for the same ligand but delivers an activating rather than inhibitory signal. By blocking TIGIT with a monoclonal antibody, more PVR becomes available to engage DNAM-1, tilting the balance of signals toward immune activation rather than suppression. This mechanism is being explored primarily in oncology, where tumors exploit checkpoint receptors like TIGIT to evade immune attack, often alongside other checkpoints such as PD-1. Because TIGIT and PD-1 operate through distinct signaling routes, blocking both is thought to produce more complete restoration of immune function than blocking either alone. The antibody described here is engineered to be "Fc-silent," meaning it is designed not to trigger antibody-dependent depletion of the very immune cells expressing TIGIT, preserving their numbers while still interrupting the inhibitory signal.