Figure 9.
(A) Coronal section of the brain of severe combined immunodeficient (SCID) mouse at expiration following the implantation of 500,000 human U87 glioma cells in the caudate-putamen nucleus (CPN), and immunostained with the 528 monoclonal antibody (MAb) against the human epidermal growth factor receptor (EGFR). Panel (A) reprinted by permission from Zhang et al. (2002). (B) Section of SCID mouse brain at expiration after the implantation of 500,000 human U87 glioma cells in the CPN, and immunostained with the 8D3 MAb against the mouse transferrin receptor (TfR). The brain tumor-bearing mice were treated with weekly injections of saline starting 5 days after tumor implantation. Capillaries originating from normal mouse brains are seen vascularizing the human U87 tumor (*). (C) Survival of SCID mice following the implantation of 500,000 human U87 glioma cells in the CPN at day 0. Starting at 5 days after tumor implantation, the mice were treated with weekly IV injections of either saline or THLs doubly targeted with the 8D3 MAb against the mouse TfR, and the 83–14 MAb against the HIR. The THLs encapsulated a plasmid DNA that encoded a 29 nucleotide (nt) short interfering RNA (shRNA) that targeted nucleotides 2,529–2,557 of the human EGFR mRNA. The plasmid expression of the shRNA leads to RNA interference (RNAi) of the EGFR transcript in the brain tumor. The weekly injection dose of plasmid DNA was 5 μg/mouse. (D) Section of SCID mouse brain at expiration after the implantation of 500,000 human U87 glioma cells in the CPN, and immunostained with the 8D3 MAb against the mouse transferrin receptor (TfR). Starting at 5 days after tumor implantation, the mice were treated with weekly injections of the THLs doubly targeted with the TfRMAb and HIRMAb and encapsulating the plasmid DNA encoding the human EGFR mRNA-specific shRNA. There is an 80% reduction in capillary density in the tumor of the RNAi treated mice, as compared to the saline-treated mice (panel B). Panels (B–D) reprinted by permission from Zhang et al. (2004b).