T-cell immunoreceptor with Ig and ITIM domains (TIGIT) (TIGIT)

T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is a co-inhibitory receptor belonging to the immunoglobulin superfamily, primarily expressed on activated T cells, Natural Killer (NK) cells, and regulatory T cells (Tregs) (UniProt Q495A1). It plays a critical role in immune homeostasis by competing with the costimulatory receptor CD226 (DNAM-1) for binding to shared ligands, most notably CD155 (PVR) and CD112 (PVRL2), which are frequently upregulated on the surface of cancer cells (PubMed: 24951006). When TIGIT binds to these ligands, it delivers an inhibitory signal via its ITIM domain that dampens T-cell and NK-cell effector functions, such as cytokine production and cytotoxicity, while promoting the suppressive activity of Tregs (PubMed: 19011627). In the tumor microenvironment, high TIGIT expression is often associated with T-cell exhaustion and poor prognosis, making it a key target for cancer immunotherapy (PubMed: 32165435). Rilvegostomig (AZD2936) is a humanized bispecific antibody designed to simultaneously inhibit TIGIT and Programmed cell death protein 1 (PD-1), aiming to provide a more potent reversal of immune suppression than monotherapy (AstraZeneca, 2023). By blocking both pathways, these agents seek to restore the anti-tumor activity of exhausted immune cells and improve clinical outcomes in patients with advanced solid tumors (ClinicalTrials.gov: NCT04995523).

Other names

VSIG9VSTM3WUCAMV-set and transmembrane domain-containing protein 3V-set and immunoglobulin domain-containing protein 9

Rilvegostomig is a bispecific antibody that concurrently targets TIGIT and PD-1; it blocks the interaction of TIGIT with its ligands (CD155 and CD112) and PD-1 with its ligands (PD-L1 and PD-L2), thereby preventing inhibitory signaling and enhancing anti-tumor T-cell and NK-cell activity (AstraZeneca, 2023; PubMed: 32165435).