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 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.
Schlingensiepen
Karl-Hermann
KH
Antisense Pharma GmbH, Josef-Engert-Str. 9, 93053 Regensburg, Germany. publications@antisense-pharm.com
Schlingensiepen
Reimar
R
Steinbrecher
Andreas
A
Hau
Peter
P
Bogdahn
Ulrich
U
Fischer-Blass
Birgit
B
Jachimczak
Piotr
P
D000818:Animals; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006131:Growth Inhibitors / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000627:therapeutic use*; D013873:Thionucleotides / Q000235:genetics / Q000627:therapeutic use*; D053781:Transforming Growth Factor beta2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
D006131:Growth Inhibitors; D009838:Oligodeoxyribonucleotides; D013873:Thionucleotides; D053781:Transforming Growth Factor beta2; C525712:Trabedersen