Histone deacetylase inhibitor, LBH589, synergizes with an immunotherapy treatment in an in vivo murine brain tumor model (41.35)

Abstract

Abstract Cancer immunotherapy treatments may show low response rates due to an anti-apoptotic tumor environment. We hypothesized a treatment of immunotherapy and histone deacetylase inhibitor, LBH589, could induce tumor cell expression of pro-apoptotic molecules and sensitize these cells to immune mediated cell death. Treatment with adoptive transfer immunotherapy and LBH589 resulted in synergistically reduced s.c. tumor burden, and prolonged survival in an intracranial tumor model. In vivo studies in non-tumor bearing mice treated with this combination therapy showed a 2-fold increase in the number of adoptively transferred cells in comparison to an immunotherapy alone treatment group. Furthermore, combination treatment also showed a 2-fold increase in ex vivo interferon-γ secretion with and without stimulation of hgp100 peptide in comparison to an immunotherapy alone group. However, overall levels of histone 3 lysine acetylation in these adoptively transferred CD8+ T-cells do not change between treatment groups. Our results suggest LBH589 enhances immunotherapy treatment by decreasing tumor burden and increasing survival in a murine melanoma brain tumor model. Furthermore, treatment with LBH589 increases CD8+ T-cell secretion of interferon-γ in the absence and presence of peptide, and this does not appear to be caused by a change in overall histone 3 lysine acetylation levels.