The epigenetic immunomodulator, HBI-8000, enhances the response and reverses resistance to checkpoint inhibitors.

ABSTRACT:

Background

Treatment with immune checkpoint inhibitors (ICIs) targeting CTLA-4 and the PD-1/PD-L1 axis is effective against many cancer types. However, due in part to unresponsiveness or acquired resistance, not all patients experience a durable response to ICIs. HBI-8000 is a novel, orally bioavailable class I selective histone deacetylase inhibitor that directly modifies antitumor activity by inducing apoptosis, cell cycle arrest, and resensitization to apoptotic stimuli in adult T cell lymphoma patients. We hypothesized that HBI-8000 functions as an epigenetic immunomodulator to reprogram the tumor microenvironment from immunologically cold (nonresponsive) to hot (responsive).

Method

Mice bearing syngeneic tumors (MC38 and CT26 murine colon carcinoma and A20 B-cell lympho

SUBMITTER: Bissonnette RP 

PROVIDER: S-EPMC8404302 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature