An anti-transferrin receptor antibody enhanced the growth inhibitory effects of chemotherapeutic drugs on human glioma cells

Transferrin receptor (TfR) has been used as a target for antibody-based therapy of cancer. Anti-TfR antibody together with chemotherapeutic drugs has potential for cancer therapy. In this study, we investigated the in vitro anti-tumor effects of the anti-TfR monoclonal antibody (mAb), 7579, alone or in combination with Nimustine, a chemotherapeutic drug, on the gliomas cell lines U251 and U87MG. Our results indicated that 7579 alone dramatically down-regulated surface expression of TfR on tumor cells and induced S phase accumulation and apoptosis of tumor cells. Compared with 7579 or Nimustine used alone, the combination of 7579 with Nimustine demonstrated enhanced growth inhibitory effect on tumor cells. PI (Propidium iodide)/Annexin V staining analyzed by FCM (flow cytometry) demonstrated that 7579 enhanced the cytotoxic effects of chemotherapeutic drug on tumor cells, indicating the therapeutic effect of 7579 was mediated mainly by promoting tumor cell necrosis. Using the median-effect/combination-index isobologram method, we further evaluated the nature of 7579/chemotherapeutic drug interactions. Synergistic interaction was observed for combination of 7579 with Nimustine. Our study provides additional evidence to develop combination therapies of anti-TfR mAbs-plus chemoimmunotherapy for gliomas.

Research Highlights► We showed that glioma specimens as well as cell lines exhibited abundant expression of TfR, and that its expression positively correlated with tumor grade. ► 7579 mAb could significantly marked S phase arrest and induced apoptosis in mAb-treated tumor cells. ► MAb enhanced the inhibition effect of proliferation of Nimustine on tumor cells and Nimustine exhibited synergistic cytotoxic effects in combination with mAb.