Even with current standard-of-care
therapies, the prognosis for patients with
malignant gliomas is very poor and several new treatment modalities for
glioblastomas are currently under investigation. Given the role of TGF-β in
gliomas, anti-TGF-β strategies against
gliomas are currently being investigated. Biodistribution of intravenously injected AF680-labeled 1D11, a pan-neutralizing TGF-β antibody, was monitored in mice bearing either subcutaneous or orthotopic
gliomas using in vivo imaging and fluorescence microscopy. AF680-labeled 1D11 entered both the subcutaneous and intracranial
tumors and the antibody was detected within the
tumor tissue for several days whereas only low fluorescence was found in organs. The effects of 1D11 on subcutaneous versus orthotopic U87MG and GL261
gliomas in immunocompetent C57BL/6J versus immunodeficient CD1-Foxn1nu mice were observed by direct
tumor size measurement, H&E staining and immunohistochemistry. Treatment of immunocompetent mice bearing subcutaneous GL261
tumors with 1D11 resulted
in complete remission. In immune deficient mice, the growth of subcutaneous GL261
tumors was increased following treatment with 1D11. Intracranially implanted
gliomas in C57Bl/6J mice showed no size reduction after 1D11 treatment but there was reduced invasion of the
glioma cells into the adjacent normal brain. Together these data demonstrate that TGF-β plays different roles in combating the
tumor depending on subcutaneous versus orthotopic implantation site.