MGN1703 induces type I interferon in the colon

Background & Aims: TLR9 agonists (e.g. MGN1703) are used to treat colorectal and other cancers in clinical trials, yet the impacts of these drugs in human intestines remain unknown. This together with the fact that there are more potential indications for TLR9 agonist therapy (e.g. ulcerative colitis and HIV), led us to investigate the impact of MGN1703 on intestinal homeostasis and HIV persistence in HIV positive individuals.Methods: Sigmoid biopsies were collected (baseline and week 4) from 11 outpatient participants in a single-arm, phase 1b/2a study where HIV+ adults on antiretroviral therapy received MGN1703 (60 mg s.c.) twice weekly for 4 weeks. In fixed tissue sections, we quantitated cell profiles positive for interferon-stimulated and inflammatory proteins. Remaining biopsy tissue was digested and percoll-enriched intestinal mononuclear cells were obtained for virological and immunological analyses. The microbiome was quantitated in stool samples (baseline and Results: RNASeq revealed 248 significantly regulated genes (FDR<0.05) including many type I interferon-stimulated genes.