Tiragolumab and TIGIT: Pioneering the Next Era of Cancer Immunotherapy

Kosar Ghasemi^*

• Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Tiragolumab, a monoclonal antibody (mAb) targeting T cell immunoreceptor with Ig and ITIM 2 domains (TIGIT), represents a novel approach in cancer immunotherapy. TIGIT, an 3 immunological checkpoint receptor, suppresses T cell activation and promotes immune evasion 4 in various cancers. By inhibiting TIGIT, Tiragolumab enhances T cell-mediated anti-tumor 5 immunity, particularly when combined with programmed cell death-1 (PD-1) and programmed 6 death-ligand 1 (PD-L1) inhibitors. This synergy arises from complementary mechanisms, 7where TIGIT blockade reduces CD155-mediated suppression, amplifying PD-1/PD-L1-driven 8 T cell activation. Phase II and III trials, including the CITYSCAPE trial for non-small cell lung 9 cancer (NSCLC), have shown improved objective response rates (37% vs. 21% with PD-L1 10 inhibitor monotherapy) and progression-free survival (PFS), with manageable adverse effects. 11However, the potential of other checkpoint inhibitors, such as Lymphocyte Activation Gene 3 12 (LAG3), T-cell immunoglobulin and mucin domain-3 (TIM-3), or cytotoxic T-lymphocyte-13 associated protein 4 (CTLA-4), remains underexplored compared to TIGIT. This review 14 summarizes TIGIT's molecular mechanisms, preclinical and clinical data, and limitations, 15 including resistance mechanisms (e.g., upregulation of alternative checkpoints), biomarker 16 development, and the need for broader investigation into alternative inhibitors to optimize 17 combination therapies for personalized, durable cancer treatment.