Cooperative Immune-Mediated Mechanisms of the HDAC Inhibitor Entinostat, an IL15 Superagonist, and a Cancer Vaccine Effectively Synergize as a Novel Cancer Therapy.

ABSTRACT:

Purpose

Immunotherapy has demonstrated clinical efficacy in subsets of patients with solid carcinomas. Multimodal therapies using agents that can affect different arms of the immune system and/or tumor microenvironment (TME) might increase clinical responses.

Experimental design

We demonstrate that entinostat, a class I histone deacetylase inhibitor, enhances the antitumor efficacy of the IL15 superagonist N-803 plus vaccine in 4T1 triple-negative breast and MC38-CEA colon murine carcinoma models. A comprehensive immune and gene-expression analysis was performed in the periphery and/or TME of MC38-CEA tumor-bearing mice.

Results

Although N-803 plus vaccine induced peripheral CD8⁺ T-cell activation and cytokine production, there was no reduction in tumor bur

SUBMITTER: Hicks KC 

PROVIDER: S-EPMC8274944 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature