期刊
CYTOKINE & GROWTH FACTOR REVIEWS
卷 17, 期 1-2, 页码 129-139出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.cytogfr.2005.09.002
关键词
TGF-beta; high-grade gliomas; pancreatic carcinoma; malignant melanoma; antisense oligodeoxynucleotides
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-beta 2 by the antisense oligodeoxynuclcotide 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-beta 2 suppression as a promising therapeutic approach for malignant tumor therapy. (c) 2005 Elsevier Ltd. All rights reserved.
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