Abstract
Despite remarkable advances in cancer research, patients with malignant tumors such as high-grade glioma or advanced pancreatic carcinoma still face a poor prognosis. Because of the severe morbidity and mortality of such malignant tumor types, the identification of suitable molecular drug targets for causal treatment approaches is an important area of current research. Transforming growth factor-beta 2 (TGF-β2) is an attractive target because it regulates key mechanisms of carcinogenesis, in particular immunosuppression and metastasis, and is frequently overexpressed in malignant tumors. Here we describe the development of the antisense phosphorothioate oligodeoxynucleotide trabedersen (AP 12009) which was designed for the specific inhibition of TGF-β2 biosynthesis. In vitro and in vivo experiments confirmed the mode of action, efficacy and tolerability of trabedersen and paved the way for clinical studies. In patients with high-grade glioma, intratumoral treatment with trabedersen is currently evaluated in a pivotal, randomized and activecontrolled phase III study. Intravenous application of trabedersen for the treatment of patients with advanced pancreatic carcinoma, metastasizing melanoma, or metastatic colorectal carcinoma is assessed in a currently ongoing phase I/II dose escalation study.
Keywords: Transforming growth factor beta, gene silencing, antisense oligonucleotide, cancer, immunosuppression, highgrade glioma, pancreatic cancer, molecular drug targets, metastatic colorectal carcinoma, intratumoral treatment, tumor cell growth, autoimmune or cancer diseases, mammalian genomes, latent TGF-β binding protein (LTBP)
Current Pharmaceutical Biotechnology
Title: The Antisense Oligonucleotide Trabedersen (AP 12009) for the Targeted Inhibition of TGF-β2
Volume: 12 Issue: 12
Author(s): Frank Jaschinski, Tanja Rothhammer, Piotr Jachimczak, Christian Seitz, Anneliese Schneider and Karl-Hermann Schlingensiepen
Affiliation:
Keywords: Transforming growth factor beta, gene silencing, antisense oligonucleotide, cancer, immunosuppression, highgrade glioma, pancreatic cancer, molecular drug targets, metastatic colorectal carcinoma, intratumoral treatment, tumor cell growth, autoimmune or cancer diseases, mammalian genomes, latent TGF-β binding protein (LTBP)
Abstract: Despite remarkable advances in cancer research, patients with malignant tumors such as high-grade glioma or advanced pancreatic carcinoma still face a poor prognosis. Because of the severe morbidity and mortality of such malignant tumor types, the identification of suitable molecular drug targets for causal treatment approaches is an important area of current research. Transforming growth factor-beta 2 (TGF-β2) is an attractive target because it regulates key mechanisms of carcinogenesis, in particular immunosuppression and metastasis, and is frequently overexpressed in malignant tumors. Here we describe the development of the antisense phosphorothioate oligodeoxynucleotide trabedersen (AP 12009) which was designed for the specific inhibition of TGF-β2 biosynthesis. In vitro and in vivo experiments confirmed the mode of action, efficacy and tolerability of trabedersen and paved the way for clinical studies. In patients with high-grade glioma, intratumoral treatment with trabedersen is currently evaluated in a pivotal, randomized and activecontrolled phase III study. Intravenous application of trabedersen for the treatment of patients with advanced pancreatic carcinoma, metastasizing melanoma, or metastatic colorectal carcinoma is assessed in a currently ongoing phase I/II dose escalation study.
Export Options
About this article
Cite this article as:
Jaschinski Frank, Rothhammer Tanja, Jachimczak Piotr, Seitz Christian, Schneider Anneliese and Schlingensiepen Karl-Hermann, The Antisense Oligonucleotide Trabedersen (AP 12009) for the Targeted Inhibition of TGF-β2, Current Pharmaceutical Biotechnology 2011; 12 (12) . https://dx.doi.org/10.2174/138920111798808266
DOI https://dx.doi.org/10.2174/138920111798808266 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
Call for Papers in Thematic Issues
Artificial Intelligence in Bioinformatics
Bioinformatics is an interdisciplinary field that analyzes and explores biological data. This field combines biology and information system. Artificial Intelligence (AI) has attracted great attention as it tries to replicate human intelligence. It has become common technology for analyzing and solving complex data and problems and encompasses sub-fields of machine ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Safety of Multi-Targeted Kinase Inhibitors as Monotherapy Treatment of Cancer: A Systematic Review of the Literature
Current Drug Safety microRNA, Cancer and Cancer Chemoprevention
Current Molecular Pharmacology Molecular Fundamentals and Rationale for Immunotherapy in Metastatic Melanoma Treatment
Clinical Cancer Drugs Gynaecological Cancer Diagnostics: 99mTc-Cisplatin Complex as a Future Approach for Early, Prompt and Efficient Diagnosis of Gynaecological Cancer
Current Medical Imaging CD133+ Glioblastoma Stem-Like Cells Induce Vascular Mimicry in Vivo
Current Neurovascular Research Therapeutic Targeting of Apoptotic Pathways: Novel Aspects in Pancreatic Cancer
Current Pharmaceutical Biotechnology Nongenomic Actions of Thyroid Hormones: From Basic Research to Clinical Applications. An Update
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Mitochondria in Cancer Stem Cells: A Target for Therapy
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Exploring siRNA Umpired Nanogels: A Tale of Barrier Combating Carrier
Current Pharmaceutical Design Design and Synthesis of Novel Thiosemicarbazones as Potent Anti-breast Cancer Agents
Letters in Drug Design & Discovery Resistance of Cancer Cells to Targeted Therapies Through the Activation of Compensating Signaling Loops
Current Signal Transduction Therapy Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer
Current Medicinal Chemistry Altered Expression of microRNAs in Serum Extracellular Vesicles in Rats with Severe Burns during Shock Stage
Current Molecular Medicine The Identification and Biochemical Properties of the Catalytic Specificity of a Serine Peptidase Secreted by Aspergillus fumigatus Fresenius
Protein & Peptide Letters Pharmacogenetics and Inflammatory Bowel Disease
Current Pharmacogenomics and Personalized Medicine <sup>68</sup>Ga-labeled HBED-CC Variant of uPAR Targeting Peptide AE105 Compared with <sup>68</sup>Ga-NODAGA-AE105
Anti-Cancer Agents in Medicinal Chemistry Different Treatment Strategies for Pediatric Brain Tumors
Current Pediatric Reviews Stable Expression of the Sodium/Iodide Symporter (NIS) for anti-Cancer Gene Therapy of Glioma Cells Using a Third Generation Self-Inactivating Lentiviral Vector System in Combination with 211At
Current Radiopharmaceuticals Antiangiogenic Resistance and Cancer Metabolism: Opportunities for Synthetic Lethality
Current Drug Targets Diazenyl Derivatives as Therapeutic and Diagnostic Agents Acting on Central Nervous System
Central Nervous System Agents in Medicinal Chemistry