The study, “IL-7 receptor influences anti-TNF responsiveness and T cell gut homing in inflammatory bowel disease,” was published in the Journal of Clinical Investigation. OSE Immunotherapeutics is developing OSE-127 in collaboration with Servier.
OSE-127 is a humanized monoclonal antibody targeting the interleukin-7 receptor (IL-7R). Interleukin-7 (IL-7), which can promote chronic inflammation, is a protein secreted by the immune system that binds to IL-7R and regulates T-cell (a type of immune cell) activity.
In those who did not benefit from anti-TNF therapy, elevated levels of IL-7 and IL-7R also were detected in colon biopsies obtained before starting anti-TNF treatment. This suggests that IL-7 and IL-7R levels may predict the effectiveness of anti-TNF treatments, the researchers said.
Laboratory studies also showed that human IL-7 was able to increase the expression of specific receptor proteins on T-cell surfaces that promote gut-homing — a mechanism that increases the T-cells’ attraction to the inflamed regions in the gut. For IBD patients, an increase in T-cell gut-homing specificity means further damage and inflammation.
The team used a humanized mouse model of IBD to evaluate the impact of OSE-127 treatment. A humanized mouse is a genetically modified mouse that has functioning human genes, tissues, cells, or organs. In this case, the mice expressed human T-cells.
They found that OSE-127 treatment significantly reduced gut-homing of human T-cells to the inflamed colon in the humanized mouse. By blocking IL-7R, OSE-127 prevented further destruction of the mucosal lining in the colon of the animals.
Investigators evaluated OSE-127 in ex-vivo (in the lab) experiments using colon biopsies from IBD patients. They noted that mucosal T-cells produced significantly lower amounts of gamma interferon — an inflammatory protein secreted by immune cells — after the colon biopsy samples were treated with OSE-127.
“These findings confirm a novel and differentiated mechanism of action of full-antagonist of IL-7R OSE-127. They support the potential of this compound to be a relevant therapy in chronic inflammatory bowel diseases where there is a high unmet medical need,” Nicolas Poirier, chief scientific officer of OSE Immunotherapeutics, said in a press release.
A Phase 1 clinical trial evaluating the safety and tolerability of ascending doses of OSE-127 in 63 healthy volunteers is underway.
“OSE-127 is currently being evaluated in a Phase 1 clinical trial, and we look forward to further exploring the product’s potential through our ongoing partnership with Servier,” Poirier said.
The study was conducted by a multinational team, led by researchers from OSE Immunotherapeutics.
“We would like to warmly thank our team, the network of renowned experts and clinicians and all international and French institutions for their commitment to this work,” Poirier added.
Servier plans to also develop OSE-127 for the treatment of Sjögren’s syndrome.
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