ITOC2 – 031. Immunomodulatory characteristics of Resminostat, a novel HDAC inhibitor in phase II clinical development

Abstract

Background Anti-cancer effects of HDAC inhibitors were shown to rely on an intact immune system. Additionally, combination of HDAC inhibitors with different cancer immunotherapy approaches was shown to be successful, suggesting that HDAC inhibition itself may engage and mediate an anti-tumoural immune response during cancer therapy. Aim Evaluation of immunomodulating effects of the HDAC inhibitor Resminostat, potentially contributing to its anti-tumoural activity. Method Resminostat effects on mechanisms affecting anti-tumoural immune responses were analysed in hepatocellular HepG2, Huh7, and SNU475 and adenocarcinomic A549 cells. Results Resminostat strongly reduced the expression of immunosuppression mediating enzymes, IDO1 and ARG1. Additionally, Resminostat considerably enhanced the expression of NKG2D ligands, MHC class I molecules, and several cancer testis antigens on several tumour cell lines. Interestingly, Resminostat was also able to up-regulate the expression of MHC class II and co-stimulatory molecule 4-1BBL. Discussion&conclusions Resminostat showed promising immunomodulatory effects demonstrating potential synergism with immunotherapy approaches using opsonizing antibodies (e.g. rituximab), immunostimulating agents (e.g. cytokines, stimulating antibodies, TLR ligands), and immune checkpoint blockers (PD1/PDL1 and CTLA-4 inhibitors).