Linus[a]
Cytokine Growth Factor Rev. 2005 Dec 22
Targeted tumor therapy with the TGF-beta2 antisense compound AP 12009.
Schlingensiepen KH, Schlingensiepen R, Steinbrecher A, Hau P, Bogdahn U, Fischer-Blass B, Jachimczak P.
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.