Related Experiment Video
Updated: Jun 6, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Tumor localization of an anti-TGF-β antibody and its effects on gliomas
Petra Hülper1, Walter Schulz-Schaeffer, Christian Dullin
1Department of Pediatrics I, University Medical Center Göttingen, Robert-Koch-Str. 40, D-37099 Göttingen, Germany. huelper@med.uni-goettingen.de
Abstract:
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.
Insights
Anti-transforming growth factor-beta (TGF-β) antibody 1D11 showed promising results in subcutaneous glioma models but had varied effects in orthotopic models, indicating site-specific roles for TGF-β in glioma progression.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Malignant gliomas, including glioblastomas, have a poor prognosis despite standard therapies.
- Transforming growth factor-beta (TGF-β) is implicated in glioma development, making anti-TGF-β strategies a focus of research.
Purpose of the Study:
- To investigate the biodistribution and efficacy of a pan-neutralizing TGF-β antibody (1D11) in preclinical glioma models.
- To determine the influence of tumor implantation site (subcutaneous vs. orthotopic) and host immunity on 1D11 treatment outcomes.
Main Methods:
- AF680-labeled 1D11 antibody biodistribution was assessed in mice with subcutaneous or orthotopic gliomas using in vivo imaging and fluorescence microscopy.
- Tumor growth and invasion were evaluated in immunocompetent and immunodeficient mice bearing U87MG or GL261 gliomas via tumor measurement, H&E staining, and immunohistochemistry.
Main Results:
- AF680-labeled 1D11 successfully localized to both subcutaneous and intracranial tumors, with sustained presence in tumor tissue.
- 1D11 treatment led to complete remission in immunocompetent mice with subcutaneous GL261 gliomas.
- Conversely, 1D11 treatment increased subcutaneous GL261 tumor growth in immunodeficient mice.
- Intracranial gliomas showed no size reduction but exhibited reduced invasion into adjacent brain tissue following 1D11 treatment.
Conclusions:
- TGF-β plays distinct roles in glioma progression depending on the tumor's location (subcutaneous vs. orthotopic).
- The host immune status significantly influences the therapeutic efficacy of anti-TGF-β therapy in gliomas.
- Targeting TGF-β may offer a viable therapeutic strategy for gliomas, but treatment optimization requires consideration of tumor microenvironment and immune context.
