Targeted tumor therapy with the TGF-beta 2 antisense compound AP 12009 |
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Authors: | Schlingensiepen Karl-Hermann Schlingensiepen Reimar Steinbrecher Andreas Hau Peter Bogdahn Ulrich Fischer-Blass Birgit Jachimczak Piotr |
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Institution: | Antisense Pharma GmbH, Josef-Engert-Str. 9, 93053 Regensburg, Germany. publications@antisense-pharm.com |
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Abstract: | 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. |
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