Here, we generated a fully human Fc-muted immunoglobulin (Ig)G4 BsAb HK010 targeting PD-L1 and 4-1BB to activate 4-1BB signaling strictly dependent on PD-L1, and to simultaneously block PD-1/PD-L1 signaling within the tumor microenvironment (TME). This evidence concerns the gene PDCD1 and neoplasm.