Week 4, September 2024: Anti-TIGIT Therapies

T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) is an immune receptor that plays a key role in suppressing T-cell activation and proliferation. As a newly identified checkpoint, it is highly expressed on various immune cells, including CD4+ and CD8+ T cells, NK cells, Tregs, and TILs. It plays a role in NK cell and T cell exhaustion, particularly in cancer. TIGIT’s primary ligand, CD155, is a key target for immunotherapy, with studies showing that cancer treatment responses to anti-PD-1 therapy are linked to CD155 rather than TIGIT.

However, anti-TIGIT therapies have failed in numerous clinical trials this past year, such as Roche’s tiragolumab, Merck’s vibostolimab, Gilead Sciences’ domvanalimab, and Bristol Myers Squibb’s AGEN1777. Despite the disappointing results, iTeos Therapeutics and GSK have presented positive results for their anti-TIGIT drug, garnering some much needed excitement at the ESMO (European Society for Medical Oncology) conference this September. 

Currently in development by iTeos Therapeutics and GSK, Belrestotug (EOS-448) is an IgG4 mAb aimed to treat lung cancer. It is the only TIGIT program that has gone through the FDA’s Project Optimus, which aims to reform the dose optimization and dose selection paradigm in oncology drug development. Currently, it is in Phase 3 trials.