The T-cell immunoglobulin and mucin-domain containing-3 (TIM3), encoded by the *HAVCR2* gene, is an immune checkpoint receptor expressed on activated T cells, natural killer (NK) cells, dendritic cells, and macrophages. It regulates immune tolerance and contributes to T-cell exhaustion in chronic infections and cancers. TIM3 interacts with ligands such as phosphatidylserine (exposed on apoptotic cells), galectin-9. HMGB1. and CEACAM1. modulating immune responses through inhibitory signaling pathways. In healthy contexts, TIM3 helps maintain immune homeostasis by suppressing excessive inflammation. However, tumors often exploit TIM3 upregulation to evade immune surveillance, making it a therapeutic target.
TIM3 antibodies are designed to block these inhibitory interactions, thereby restoring T-cell function and enhancing anti-tumor immunity. Preclinical studies show that TIM3 blockade synergizes with anti-PD-1/PD-L1 therapies, addressing resistance to single-agent checkpoint inhibitors. Clinical trials are evaluating TIM3-targeting monoclonal antibodies (e.g., cobolimab, sabatolimab) in advanced cancers, often in combination regimens. Challenges include identifying predictive biomarkers and managing immune-related adverse events. Research also explores TIM3's role in autoimmune diseases, where its inhibition may exacerbate pathology, highlighting context-dependent therapeutic implications. Overall, TIM3 antibodies represent a promising frontier in immuno-oncology, with ongoing efforts to optimize their clinical utility.