3:00 PM Abstract No. 108 ■ FEATURED ABSTRACT Combination irreversible electroporation ablation and local delivery of indoleamine 2,3-dioxygenase inhibitor loaded multifunctional carriers for treating prostate cancer

Abstract

Irreversible electroporation (IRE) ablation and follow-up elevating immune response endow IRE-based therapy as an attractive approach for cancer treatment. This study aimed to evaluate whether IRE combining indoleamine 2,3-dioxygenase inhibitor (IDOi, Epacadostat) loaded iron oxide nanocarriers (IDOi-INCs) can serve as a magnetic resonance imaging (MRI)–guided local ablation strategy for enhancing prostate cancer immunotherapy. IDOi-INCs was formed by hydrophobic interaction between IDOi and INCs and was stabled by coating sodium cholate hydrate. In vitro cell assays in Tramp-C1 cancer cells observed IDOi-INCs enhanced IRE induced cancer cell death. T2-weighted MRI was utilized to observe the distribution of locally injected IDOi-INCs inside tumor (Tramp-C1 tumor-bearing male C57BL/6 mice). While tumor volume reached 100 cm3, mice were divided into six groups: PBS, IDOi-INCs, PBS plus IRE (ten 100-μsec and 1200 V/cm pulses), IDOi plus IRE, INCs plus IRE, IDOi-INCs plus IRE (n = 5). Finally, after various treatment, tumor response was monitored by recording tumor size and analyzing tumor histology. Tumor microenvironment was evaluated by the quantification of T lymphocytes. Cluster structure and size of IDOi-INCs were confirmed with the transmission electron microscope and dynamic light scattering. In vitro study, DOi-INCs efficiently attached to the membranes of Tramp-C1 cells which may contribute to enhance in vitro and in vivo cell-killing effect of IRE. In vivo study with T2W MRI showed that 12 h post infusion of IDOi-INCs is an ideal time window for the following IRE ablation. IDOi-INCs plus IRE among experimental groups showed the best treatment outcomes after 14 days post IRE ablation. The analysis of tumor responses and histology verified that IRE ablation was enhanced by combing INCs or IDOi-INCs. Increased infiltration of CD8+ T cells after IRE ablation and an elevated ratio of CD8+ T cells to regulatory T cells were achieved in a combination of locally delivered IDOi-INCs and IRE. The combination of performing immunogenic ablation and modulating local immunosuppressive tumor microenvironment would be an effective approach for treating prostate cancer.