Herein, we innovatively design a novel nanobody-based trispecific T cell engager (Nb-TriTE) that is composed of two Nbs targeting CD3ε on T cells and tumor associated antigen (TAA) on cancer-associated fibroblasts (CAFs), and the exclusive use of a third Nb targeting immune checkpoint as building blocks of the immunosuppressive signaling pathway. The gene discussed is CD3E; the disease is cancer.