Abstract 1745: NPY1 receptor specific peptide-drug-conjugates as novel treatment for metastatic breast cancer

Abstract

Abstract The NPY1 receptor is a known marker for breast cancer that was characterized first at the university hospital Bern by the group of Reubi. In healthy breast tissue the NPY2 receptor (NPY2R) can be found, expression of which is switched to the NPY1R in tumor tissues (Reubi et al., Cancer Res. 2001, 61, 4636-4641). Particularly high NPY1R densities were also found in tumor biopsies of patients suffering from Ewing's sarcoma, which is a rare, difficult to treat juvenile bone cancer (Körner et al., Clin. Cancer Res. 2008, 14, 5043-5049.). Our own results verify these literature reports, shown on a panel of patient biopsies where nearly 50% of the tumors strongly overexpress the NPY1R, whereas NPY2R could not be detected. OntoChem has developed peptide-drug-conjugates (“CytoPep”) that are selective agonists of the NPY1 receptor. As drugs we have used tubulin binding cytolysins and maytansines. CytoPep shall be developed as novel approach to treat Ewing's sarcoma and NPY1R expressing breast cancer. We will present data on in vitro and in vivo pharmacology of these PDCs. IN particular efficacy is directly correlated with NPY1R expression levels in cells. We will also demonstrate internalization studies, showing a fast and selective internalization into NPY1R expressing cells. These in vitro data will be compared with corresponding data from ADCs such as for example trastuzumab emtansine, that show a considerably slower internalization and efficacy. Citation Format: Lutz Weber, Robert Rennert. NPY1 receptor specific peptide-drug-conjugates as novel treatment for metastatic breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1745. doi:10.1158/1538-7445.AM2015-1745