TIGIT (T cell Ig and ITIM domain) is a member of the poliovirus receptor (PVR)/Nectin family. It consists of an extracellular immunoglobulin variable domain (IgV), a type I transmembrane domain, and intracellular domains with classic immunoreceptor tyrosine-based inhibitory motif (ITIM) and immunoglobulin tyrosine tail (ITT) motifs.
CD155 (PVR) is a high-affinity ligand for TIGIT. Once the highly expressed CD155 on tumor surfaces binds to TIGIT on the surfaces of NK and T cells, their killing effect on tumor cells is inhibited. Based on the principle of the TIGIT axis and the complex immune suppression patterns in the tumor microenvironment, how to safely and effectively block TIGIT in clinical settings has become a technical challenge that many medical researchers aim to overcome, with the testing of anti-TIGIT antibody drugs being the first step towards clinical application.
Based on the aforementioned research findings, there are currently multiple TIGIT antibody developments entering clinical trials. Recent results from Roche's phase II trial of Tiragolumab show that the combination of Tiragolumab with the PD-L1 monoclonal antibody (Tecentriq) demonstrated higher objective response rates and progression-free survival compared to Tecentriq monotherapy in metastatic non-small cell lung cancer patients. The clinical trials have now progressed to phase III to further validate the drug's efficacy in a broader patient population. Additionally, several pharmaceutical companies are investing in the development of anti-TIGIT drugs, such as Merck MK-7694, Gilead AB154, and Bristol-Myers Squibb BMS-986207, which are currently undergoing phase I/II trials for initial evaluation, with hopes for successful outcomes in the future.
