Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Tim-3 is a co-inhibitory or immune checkpoint receptor that is highly expressed on dysfunctional CD8+ tumor-infiltrating lymphocytes (TILs) and intra-tumoral Treg. Anti-Tim-3 antibodies have shown efficacy as single agents in some pre-clinical tumor models and in multiple tumor models when used in combination with anti-PD-1 antibodies. Accordingly, anti-Tim-3 antibodies are currently being investigated in clinical trials. An important consideration for developing therapeutic antibodies against Tim-3 for clinical translation is that multiple ligands and ligand binding surfaces have been identified for Tim-3. We have investigated the properties of therapeutic anti-human and anti-murine Tim-3 antibodies to identify the relevant Tim-3:ligand interactions that must be disrupted for therapeutic efficacy. Using computational approaches, we have further identified the gene programs expressed by Tim-3+ TILs and begun to identify how disruption of Tim-3 either genetically or therapeutically alters these programs. Our findings provide key information for the evaluation of therapeutic anti-Tim-3 antibodies and their potential mode of action.
Credits: None available.
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