Abstract B192: The EPR effect of CDP-tubulysin in the recurrence of lung and pancreatic cancers

Abstract

Abstract Tubulysins, a tubulin-targeted class of natural compounds, are highly active in multidrug-resistant cells and potential agents to overcome clinical drug resistance in recurrent tumors. Unfortunately, the extraordinary activity of the potent tubulysins poses considerable complications for chemotherapeutic applications due to toxicity against normal cells and tissues. Nanoparticle drug delivery systems provide the potential to increase the intracellular concentration of drugs in cancer cells while avoiding toxicity in normal cells through the enhanced permeability and retention (EPR) effect. In this study, the efficacy of β-cyclodextrin-based polymeric tubulysin (CDP-tubulysin) administered by intravenous injection was tested on subcutaneous lung and pancreatic xenograft models. The single-dose pharmacokinetic study and tumor distribution of CDP-tubulysin and tubulysin alone were also determined in tumor-bearing mice. Our data demonstrated that CDP-tubulysin showed potent efficacy in treating lung and pancreatic cancers. The recurrent lung and pancreatic tumors were also regressed by treating with CDP-tubulysin but not gemcitabine. Moreover, the conjugation of CDP to tubulysin showed control-release behavior in the blood resulting in increased distribution of tubulysin in tumors. In conclusion, CDP conjugation was an effective delivery of tubulysins to avoid toxicity and provide potency in recurrent tumors through the EPR effect. Citation Format: Pei-Yi Tsai, Huei-Lin Jheng, Yen-Ju Hsieh, Yung-Jen Tsai, Michael Ahrweiler, Wolfgang Richter, Muhammad Abbas, Gianfranco Pasut, Jia-Ming Chang. The EPR effect of CDP-tubulysin in the recurrence of lung and pancreatic cancers [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B192.