1. Inhibition of TGF-β2 with AP 12009 in Recurrent Malignant Gliomas From Preclinical to Phase III Studies.
- Author
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Peter Hau, Piotr Jachimczak, Reimar Schlingensiepen, Frank Schulmeyer, Tanya Jauch, Andreas Steinbrecher, Alexander Brawanski, Martin Proescholdt, Jürgen Schlaier, Johanna Buchroithner, Josef Pichler, Gabriele Wurm, Maximilian Mehdorn, Rainer Strege, Gerhard Schuierer, Victoria Villarrubia, Franz Fellner, Olav Jansen, Thorsten Straube, and Virinder Nohria
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GLIOMAS , *CLINICAL trials , *CANCER patients , *CELLS - Abstract
Transforming growth factor-beta2 (TGF-β2) is known to suppress the immune response to cancer cells and plays a pivotal role in tumor progression by regulating key mechanisms including proliferation, metastasis, and angiogenesis. For targeted protein suppression the TGF-β2-specific antisense oligodeoxynucleotide AP 12009 was developed. In vitroexperiments have been performed to prove specificity and efficacy of the TGF-β2 inhibitor AP 12009 employing patient-derived malignant glioma cells as well as peripheral blood mononuclear cells (PBMCs) from patients. Clinically, the antisense compound AP 12009 was assessed in three Phase III-studies for the treatment of patients with recurrent or refractory malignant (high-grade) glioma WHO grade III or IV. Although the study was not primarily designed as an efficacy evaluation, prolonged survival compared to literature data and response data were observed, which are very rarely seen in this tumor indication. Two patients experienced long-lasting complete tumor remissions. These results implicate targeted TGF-β2-suppression using AP 12009 as a promising novel approach for malignant gliomas and other highly aggressive, TGF-β-2-overexpressing tumors. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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