Radioimmunoliposome targeting mesothelioma cancer stem cells

J.S. Lee, T. Huang, A. Banizs, J. He
University of Virginia, US

Keywords: immunoliposomes, cancer stem cells, mesothelioma, radiolabeling

Summary:

Malignant mesothelioma (MM) is a lethal tumor originating in the mesothelium without attractive therapies. Cancer stem cells (CSCs) in MM are critical targets responsible for tumor resistance and recurrence. The identification and characterization of CSCs may help early diagnosis and treatment of MM. The objective of this study is to develop effective radioimmunotherapy (RIT) by introducing liposomes as the delivery platform to deliver high dose of radioisotopes (177Lu) and novel antibodies (CD26 and CD24) to the target CSCs of MM. Here we show that CSCs could be identified by targeting CD26 and CD24 of MM. Small interference RNA (shRNA) caused substantial down-regulated expressions of CD26 and CD24 in MMs. CSCs sorted from H28 cells exhibited significant drug resistance and enhanced proliferative activity as well as increased invasive potential with high 18F-FDG uptake. Our RIT showed substantial effects on inhibiting proliferation, up-regulating apoptosis, and suppressing the expressions of CD26 and CD24 presumably via accumulation of 177Lu and mAbs to the tumor cells in vitro and in vivo. Thus, our results suggest that RIT utilized in the present study could be a promising therapeutic approach for treatment of CSCs in various cancers.