Engineered cytokine-antibody fusion protein to treat Inflammatory Bowel Disease.

The interleukin-2 (IL-2) protein plays an essential role in regulating the immune response and preventing the development of autoimmune disorders by supporting the growth and activity of regulatory T cells (Tregs). Promising preclinical and clinical work has demonstrated the potential for IL-2 to mitigate autoimmune diseases, including Inflammatory Bowel Disease (IBD). However, in addition to stimulating Tregs, IL-2 also stimulates effector T cells and natural killer (NK) cells, which drive inflammation and lead to autoimmune disease progression. Thus, developing a biased version of IL-2 that activates Tregs but not effector T or NK cells would represent a monumental advance for autoimmune disease therapy. A recently discovered antibody known as F5111 specifically directs the activities of IL-2 towards Tregs, while also extending its persistence in the bloodstream. We built on this work and designed a single-agent fusion protein that combines IL-2 with F5111 and demonstrated that our engineered therapeutic, called the F5111 immunocytokine (IC), selectively activated Tregs and protected mice against disease development in an IBD model. This project aims to advance the translation of F5111 IC, performing vital studies in animal models and patient samples that will catapult this molecule into clinical trials to directly benefit patients with IBD.