Targeted tumor therapy with the TGF-beta 2 antisense compound AP 12009
TGF-beta overexpression is a hallmark of various malignant tumors. This is due to the pivotal role of TGF-beta as it regulates key mechanisms of tumor development, namely immunosuppression, metastasis, angiogenesis, and proliferation. We have developed a new immunotherapeutic approach for the treatm...
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| Veröffentlicht in: | Cytokine & growth factor reviews 2006-02, Vol.17 (1-2), p.129-139 |
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| container_title | Cytokine & growth factor reviews |
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| creator | Schlingensiepen, Karl-Hermann Schlingensiepen, Reimar Steinbrecher, Andreas Hau, Peter Bogdahn, Ulrich Fischer-Blass, Birgit Jachimczak, Piotr |
| description | TGF-beta overexpression is a hallmark of various malignant tumors. This is due to the pivotal role of TGF-beta as it regulates key mechanisms of tumor development, namely immunosuppression, metastasis, angiogenesis, and proliferation. We have developed a new immunotherapeutic approach for the treatment of malignant tumors based on the specific inhibition of TGF-beta2 by the antisense oligodeoxynucleotide AP 12009. After providing preclinical proof of concept, we assessed safety and efficacy of AP 12009 in clinical phase I/II open-label dose escalation studies in high-grade glioma patients. Median survival time after recurrence exceeded the up to date literature data for chemotherapy. A phase I/II study in pancreatic carcinoma and malignant melanoma is currently ongoing. Our results implicate targeted TGF-beta2 suppression as a promising therapeutic approach for malignant tumor therapy. |
| doi_str_mv | 10.1016/j.cytogfr.2005.09.002 |
| format | Article |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Cell Line, Tumor Drug Delivery Systems - methods Gene Expression Regulation, Neoplastic - drug effects Growth Inhibitors - genetics Growth Inhibitors - therapeutic use Humans Oligodeoxyribonucleotides - genetics Oligodeoxyribonucleotides - therapeutic use Thionucleotides - genetics Thionucleotides - therapeutic use Transforming Growth Factor beta2 - antagonists & inhibitors Transforming Growth Factor beta2 - biosynthesis Transforming Growth Factor beta2 - genetics Transforming Growth Factor beta2 - secretion |
| title | Targeted tumor therapy with the TGF-beta 2 antisense compound AP 12009 |
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