PMID- 21109925 OWN - NLM STAT- MEDLINE DCOM- 20110524 LR - 20101126 IS - 1791-2423 (Electronic) IS - 1019-6439 (Linking) VI - 38 IP - 1 DP - 2011 Jan TI - Tumor localization of an anti-TGF-beta antibody and its effects on gliomas. PG - 51-9 AB - 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-beta in gliomas, anti-TGF-beta strategies against gliomas are currently being investigated. Biodistribution of intravenously injected AF680-labeled 1D11, a pan-neutralizing TGF-beta 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-beta plays different roles in combating the tumor depending on subcutaneous versus orthotopic implantation site. FAU - Hulper, Petra AU - Hulper P AD - Department of Pediatrics I, University Medical Center Gottingen, Robert-Koch-Str. 40, D-37099 Gottingen, Germany. huelper@med.uni-goettingen.de FAU - Schulz-Schaeffer, Walter AU - Schulz-Schaeffer W FAU - Dullin, Christian AU - Dullin C FAU - Hoffmann, Peter AU - Hoffmann P FAU - Harper, Jay AU - Harper J FAU - Kurtzberg, Leslie AU - Kurtzberg L FAU - Lonning, Scott AU - Lonning S FAU - Kugler, Wilfried AU - Kugler W FAU - Lakomek, Max AU - Lakomek M FAU - Erdlenbruch, Bernhard AU - Erdlenbruch B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Int J Oncol JT - International journal of oncology JID - 9306042 RN - 0 (Antibodies, Monoclonal) RN - 0 (Transforming Growth Factor beta) SB - IM MH - Animals MH - Antibodies, Monoclonal/immunology/pharmacokinetics/*pharmacology MH - Antibody Specificity MH - Brain Neoplasms/*drug therapy/immunology/pathology MH - Cell Line, Tumor MH - Glioma/*drug therapy/immunology/pathology MH - Humans MH - Immunocompetence MH - Immunohistochemistry MH - Mice MH - Mice, Inbred C57BL MH - Mice, Nude MH - Microscopy, Fluorescence MH - Neoplasm Invasiveness MH - Spectroscopy, Near-Infrared MH - Tissue Distribution MH - Transforming Growth Factor beta/*immunology MH - Xenograft Model Antitumor Assays EDAT- 2010/11/27 06:00 MHDA- 2011/05/25 06:00 CRDT- 2010/11/27 06:00 PHST- 2010/11/27 06:00 [entrez] PHST- 2010/11/27 06:00 [pubmed] PHST- 2011/05/25 06:00 [medline] PST - ppublish SO - Int J Oncol. 2011 Jan;38(1):51-9.