Targeted tumor therapy with the TGF-beta2 antisense compound AP 12009 for the treatment of advanced solid tumors

• DOI: 10.1200/jco.2006.24.18_suppl.14012
• Publication Date: 2020-03-09T19:52:56Z
• Authors: H. Oettle; T. Seufferlein; R. Schmid; T. Luger; S. Ludwig; S. Schmaus; M. Beyer; D. Fischer; M. Hafner; K. Schlingensiepen
• Keywords: Immunosuppression

14012 Background: TGF-β overexpression in advanced tumors is correlated with tumor-induced immunosuppression, proliferation and angiogenesis. Furthermore, it a key factor for induction of epithelial to mesenchymal transition (EMT), thus promoting invasion metastasis. Targeted tumor therapy by an antisense oligonucleotide has already been proven be successful therapy: AP 12009, TGF-β2-mRNA-specific oligodeoxynucleotide, shown strong clinical indication efficacy including complete lasting remissions malignant glioma. Methods: Spurred the highly encouraging data glioma anti-tumor activity wide variety preclinical assays, studies further indications were initiated. A multi-center dose-escalation phase I/II trial 12009 patients suffering from solid was started 2005. Primary endpoint assess maximum tolerated dose (MTD) as well dose-limiting toxicity (DLT). administered i.v. 14-day cycles. Results: Preclinically, human pancreatic cancer melanoma cell cultures significantly reduced TGF-β2 secretion cells, inhibited proliferation, blocked migration cells. Additionally, reversed mediated immunosuppression induced carcinoma In ongoing study, two cohorts have treated intravenously Dec Further escalations are ongoing. So far, no DLT, possibly related SAEs only seven AEs observed. MTD not yet reached. The majority received more than minimum number cycles, one them ten full First signs could also Conclusions: conclusion, results application lead form rational basis use compound targeted advanced, overexpressing tumors. [Table: see text]