Etrolizumab treatment in Crohn's disease (Bergamot) cohort 1 RNA-seq

Etrolizumab is an investigational monoclonal antibody that binds the β7 subunit of α4β7 and αEβ7 integrins. The relative contribution of α4β7 and αEβ7 to gut lymphocyte trafficking remains to be characterized. Here we show that αEβ7 is highly expressed on human intestinal CD8+ cytotoxic intraepithelial lymphocytes (IELs) and a small subset of proinflammatory CD4+ T cells. Dual blockade of α4β7 and αEβ7 reduced CD8+ T cell accumulation in the gut to a greater extent than single blockade of either pathway using a photo-convertible mouse model. αEβ7 blockade decreased T cell-epithelial interactions, increased the migratory speed and promoted egress of activated T cells. In Crohn’s disease patients treated with etrolizumab, a reduction of inflammatory genes and cytotoxic IEL gene signatures was observed. Concurrent blockade of α4β7 and αEβ7 increases reduction of cytotoxic IELs and inflammatory T cells in the gut mucosa through a stepwise inhibition of cell migration and tissue retention. The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech. RNA isolated from intestinal biopsies from a phase 3 randomized double-blind placebo-controlled 14-week trial of etrolizumab in Crohn's disease Raw data not provided due to patient privacy concerns