However, addressing the limited availability of antigen targets, the immunosuppressive TME, and the challenges related to penetrating the intricate vasculature of solid tumors remain key hurdles in the treatment of solid tumors.[16, 18, 20] In the present study, we developed a novel approach utilizing an Nb‐based dual ICP‐targeting T cell engager, Nb‐TriTE, consisting of anti‐PD‐L1, anti‐HLA‐G, and anti‐CD3ε VHH antibodies (Nbs), to overcome the limitations associated with immunotherapies for the treatment of NSCLC. This evidence concerns the gene CD3E and non-small cell lung carcinoma.