Monoclonal antibody against human Tim‐3 enhances antiviral immune response

T cell immunoglobulin and mucin domain protein 3 (Tim‐3) is an immune checkpoint inhibitor in T cells and innate immune cells. The deregulated upregulation of Tim‐3 is related to immune exhaustion in tumour and viral infection. To overcome Tim‐3‐mediated immune tolerance, we developed a novel monoclonal antibody against human Tim‐3 (L3G) and investigated its roles in inhibiting Tim‐3 signalling and overcoming immune tolerance in T cells and monocytes/macrophages. The administration of L3G to cultured peripheral blood mononuclear cells (PBMCs) significantly increased the production of IFN‐γ and IL‐2 and the expression of type I interferon. The administration of L3G also increased the production of IFN‐γ, IL‐8 and type I interferon in U937 cells and primary monocytes. We investigated the mechanisms by which L3G enhances pro‐inflammatory cytokine expression, and our data show that L3G enhances STAT1 phosphorylation in both monocytes/macrophages and T cells. Finally, in an H1N1 infection model of PBMCs and U937 cells, L3G decreased the viral load and enhanced the expression of interferon. Thus, we developed a functional antibody with therapeutic potential against Tim‐3‐mediated infection tolerance.