HER2/PD-L1 BsAb was superior to mAb and combination therapies in PBMC-“humanized” HCC1954 xenograft model. NOG mice were subcutaneously inoculated with HCC1954 cells and human PBMCs (107 cells/mouse) were injected to the tumor sites when tumor volumes reached 100 mm3. NOG mice were randomized into different groups after mean tumor volumes reached 150 mm3 and received i.v. administration of BsAb (10 mg/kg, n = 7, G4), trastuzumab (7.5 mg/kg, n = 7, G2), trastuzumab + anti-PD-L1 mAb (7.5 mg/kg +7.5 mg/kg, n = 7, G3), or isotype control (7.5 mg/kg, n = 7, G1), BIW, as indicated. A, tumor growth in PBMC-“humanized” HCC1954 xenograft model after received different treatments. B, tumor weights on the day when the group of mice were euthanized. C, tumor images on the day when the group of mice were euthanized. ∗∗p < 0.01 and ∗∗∗p < 0.001 as indicated by one-way ANOVA followed by Newman–Keuls multiple comparisons test. Data were represented as mean ± STE.