Targeted tumor therapy with the TGF-beta 2 antisense compound AP 12009

• Published in: Cytokine & growth factor reviews Vol. 17; no. 1-2; pp. 129 - 139
• Main Authors: Schlingensiepen, Karl-Hermann, Schlingensiepen, Reimar, Steinbrecher, Andreas, Hau, Peter, Bogdahn, Ulrich, Fischer-Blass, Birgit, Jachimczak, Piotr
• Format: Journal Article
• Language: English
• Published: England 01.02.2006
• 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
• ISSN: 1359-6101
• DOI: 10.1016/j.cytogfr.2005.09.002

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.