Abstract 4391: Evaluation of tumor targeting activity by elastin like polypeptide containing cell penetrating peptide and IL-4 receptor targeting peptide

Abstract

Abstract The tumor specific internalization of therapeutics drug is been a great importance for cancer therapy. Targeted macromolecular carrier has been used as drug cargos since it improve the cellular uptake of cytotoxic drug in the tumor, while preventing cellular uptake by healthy tissues. Because of favorable pharmokinetic profile, elastin like polypeptide (ELPs) has been used as macromolecular drug carrier for cancer therapy. Fusion with cell-penetrating peptides (CPPs) such as TAT, assist easy penetration and internalization of macromolecular drug conjugates into wide variety of tumor types. For therapeutic peptide to be more penetrable and more effective towards specific tumor tissue, here we have designed a chimeric polypeptide cargo, TAT-AP1-ELP containing TAT, IL-4 receptor (IL4R) targeting peptide AP-1and thermal sensitive elastin-like polypeptides (ELPs). Then it was successfully expressed and purified from E coli using inverse temperature cycling method. Cellular uptake and intracellular localization of TAT-AP1-ELP was monitored through flow cytometry and confocal microscopy. Flow cytometry analysis data shown that both TAT-AP1-ELP and TAT-ELP showed various extends of penetration ability to different cancer cells but not to normal cells. Further a greater cellular uptake was observed in IL4R highly expressing cancer cells when treated with TAT-AP1-ELP compared to TAT-ELP at 37°C in dose-dependent manner. Confocal imaging verified the better cellular accumulation of TAT-AP1-ELP than TAT-ELP in IL4R highly expressing cancer cells. Importantly, the FNR 675-labeled TAT-AP1-ELP polymer showed better tumor accumulation in MDA-MB 231 xenograft mouse model. Thus in this study we demonstrate the improved activity of CPP, fused with targeting modalities in order to enhance intra tumor accumulation of therapeutic peptides. Citation Format: Young-Jin Lee, Vijaya Sarangthem, Yun-Jae Kim, Kuen Hur, Byung-Heon Lee, Rang Woon Park. Evaluation of tumor targeting activity by elastin like polypeptide containing cell penetrating peptide and IL-4 receptor targeting peptide. [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 4391. doi:10.1158/1538-7445.AM2015-4391