Abstract 4389: Liposomes containing piperazine compounds inhibit tumor growth in a patient-derived xenograft model of glioblastoma multiforme

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Glioblastoma multiforme (GBM) is fatal in nearly all instances, and responds poorly to current standards of care. GBMs exhibit resistance to chemotherapy which leads to tumor recurrence following initial surgical debulking. We have recently developed an 80 nm liposome containing a novel hydrophobic microtubule disrupting piperazine. This novel nanostructure, called IM-1 nanobin, contains 500-1000 piperazine drug molecules encapsulated in the hydrophobic inner leaflet of the lipid bilayer in each liposome. This nanoparticle inhibited the proliferation of GBM cells in vitro, although its cytotoxicity was reduced (3-5 fold) compared to free drug dissolved in DMSO. Results from FACS analysis showed that sub-micromolar concentrations of IM-1 caused G2/M phase cell cycle arrest and apoptosis of U87 GBM cells, as well as early passage GBM cells derived from a patient-derived xenograft (PDX). In collaboration with the Northwestern Brain Tumor Institute, we have established a panel of PDX. Since these tumors are not propagated in culture, they preserve the mixture of tumor cells and stroma critical for conducting meaningful therapy response experiments. IM-1 was evaluated in GBM PDX propagated in subcutaneous and intracranial compartments. In mice bearing subcutaneous PDX tumors, IM-1 treatment delayed the growth of the tumors compared to free drug alone; orthotopic GBM PDX studies are ongoing. Our results show that a novel liposome encapsulated piperazine, IM-1, is a promising new nanostructure for development as a therapeutic for treating patients with GBM. Citation Format: Elden P. Swindell, Andrey Ugolkov, Christian Freguia, Oleksii Dubrovskyi, Patrick L. Hankins, Jeong Yang, Jeffrey J. Raizer, James P. Chandler, Charles David James, Andrew P. Mazar, Thomas V. O'Halloran. Liposomes containing piperazine compounds inhibit tumor growth in a patient-derived xenograft model of glioblastoma multiforme. [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 4389. doi:10.1158/1538-7445.AM2015-4389