Results were presented in an abstract titled, “Interleukin-7 receptor pathway controls human T cell homing to the gut and predicts response to anti-TNFα therapy in IBD,” at the recent annual congress of the American Association of Immunologists in Austin, Texas.
In an effort to learn more about these networks, researchers conducted an analysis of all the genes expressed in 500 IBD patients and compared them with those expressed in 100 healthy controls.
Researchers discovered that genes that are part of a specific signaling network — the interleukin-7 receptor (IL-7R) pathway — tend to be highly expressed in the inflamed colon tissues of patients with severe IBD who don’t respond to either immunosuppressive/corticosteroids or anti-TNFα treatment.
In fact, patients with higher levels of IL-7R and IL-7R-pathway-related gene expression in their colons prior to treatment were more likely to be nonresponsive to anti-TNFα therapy.
Researchers also found that IL-7 in humans controls the expression of certain proteins that play a role in attracting T-cells, a type of immune cell, to the gut in a process called gut homing.
Additionally, they showed that blocking the IL-7 pathway using OSE-127 in a mouse model of IBD led to a reduction in T-cell gut homing as well as inflammation of the colon. Furthermore, use of OSE-127 was associated with an increase in levels of regulatory T-lymphocytes — cells that fight inflammation.
“Our findings suggest that the failure of current treatments for IBD, including anti-TNF, may occur at least in part by dysregulated IL-7R signaling and points to the IL-7R as a relevant novel therapeutic target and biomarker to fill an unmet need in clinical IBD detection and treatment,” the researchers concluded.
Since OSE-127 specifically targets IL-7R and increases the presence of regulatory T-lymphocytes, it offers a promising approach to treat IBD.
OSE Immunotherapeutics has partnered with Servier Laboratories on developing OSE-127 up to the completion of a Phase 2 clinical trial in patients with autoimmune bowel disease and Sjögren’s syndrome.