IL-12 Enhances the Antitumor Actions of Trastuzumab via NK Cell IFN-γ Production

摘要: The antitumor effects of therapeutic mAbs may depend on immune effector cells that express FcRs for IgG. IL-12 is a cytokine stimulates IFN-γ production from NK and T cells. We hypothesized coadministration with murine anti-HER2/neu mAb (4D5) would enhance the FcR-dependent mechanisms contribute to its activity. Thrice-weekly therapy (1 μg) 4D5 mg/kg) significantly suppressed growth colon adenocarcinoma was engineered human HER2 (CT-26HER2/neu) in BALB/c mice compared result IL-12, 4D5, or PBS alone. Combination associated increased circulating levels IFN-γ, monokine induced by RANTES. Experiments IFN-γ–deficient demonstrated this necessary observed plus 4D5. Immune cell depletion experiments showed (but not CD4+ CD8+ cells) mediated treatment combination. Therapy HER2/neu-positive tumors trastuzumab tumor necrosis but did affect proliferation, apoptosis, vascularity, lymphocyte infiltration. In vitro CT-26HER2/neu revealed an intracellular signal inhibit cellular proliferation induce apoptosis. Taken together, these data suggest regression response through provide rationale cell-activating cytokines mAbs.