Newly released data from Chugai Pharmaceuticals shows their drug candidate DONQ52 potently blocks gluten-specific t-cells and is ready for continued development. So, what does this mean for the celiac disease community?  

Celiac disease is a genetic, autoimmune condition where gluten ingestion leads to an immune response that damages the small intestine.  This damage is triggered by specific immune cells (gluten-specific CD4+ T cells) that react to gluten and are activated by the HLA-DQ2.5 molecule present in 80-90% of celiac patients. In an exciting development, researchers from Chugai Pharmaceuticals in Japan evaluated the effectiveness of an antibody named DONQ52 to specifically target the HLA-DQ2.5-gluten peptide complex and block the immune response characteristic of celiac disease. 

Each participant in the study performed a gluten challenge with wheat (n=20), barley (n=10), or rye (n=14). Post gluten challenge, blood samples were analyzed for T cell immune responses to gluten peptides. The results showed that DONQ52 significantly reduced T cell responses in all individuals, with the most pronounced effect in the wheat subgroup. Importantly, DONQ52 did not affect T cell responses to non-gluten antigens, enhancing its safety profile. 

This proof-of-concept study demonstrates that targeting HLA-DQ2.5 with a specific antibody like DONQ52 can effectively block the immune response triggered by gluten, offering a potential new therapeutic approach for managing celiac disease beyond the gluten-free diet. Ongoing research continues to explore the full potential and long-term safety of this innovative approach. 

Read the full paper: A bispecific antibody targeting HLA-DQ2.5-gluten peptides potently blocks gluten-specific T cells induced by gluten ingestion in patients with celiac disease