Summary
A bioRxiv preprint describes IL-2IT, a bispecific fusion protein designed to carry IL-2 to oxidation-specific epitopes at inflamed sites. In laboratory and in vivo models, the treatment showed greater Treg selectivity and benefits in psoriasis, colitis and atherosclerosis models.
Researchers have developed a bispecific IL-2 fusion protein designed to direct immune-regulating activity to inflamed tissue. In a bioRxiv preprint posted on September 15, 2026, the team reports that the candidate, called IL-2IT or OSE-IL-2, showed bifunctional activity in laboratory experiments and improved results in in vivo models of psoriasis, colitis and atherosclerosis.
The work is a preclinical study based on cell experiments and disease models rather than a human clinical trial. The authors describe the approach as a possible “third-generation IL-2” therapy because it combines targeted delivery with the biological activity of native IL-2.
How the targeted IL-2 design works
Interleukin-2, or IL-2, is an immune-signalling protein that supports the survival and activation of regulatory T cells, known as Tregs. These cells help restrain excessive immune responses. Low-dose native IL-2 has been investigated for restoring immune regulation in autoimmune, inflammatory and neuroimmune diseases.
The new design links IL-2 to a single-chain antibody that recognises oxidation-specific epitopes, or OSEs. These molecular features are produced by oxidative modification and are found abundantly at sites of inflammation, according to the preprint. The antibody component is intended to guide the fusion protein to those sites, while the IL-2 component acts on immune cells.
The researchers describe the molecule as bifunctional because both parts are intended to contribute to its activity: antibodies against OSEs can themselves have effects relevant to inflammation, while low-dose IL-2 can promote regulatory immune activity. The design also aims to preserve native IL-2 signalling rather than replacing it with a heavily altered cytokine.
Results in laboratory and disease models
In vitro experiments showed that IL-2IT retained the biological activities of both targeting components, according to the authors. In vivo, the fusion protein produced greater specificity for activating Tregs over effector T cells, which are immune cells that promote active immune responses. The researchers attribute this preference to a conformation-dependent change in how the molecule engages the IL-2 receptor.
The preprint also reports targeted localisation of IL-2IT in inflamed tissues in models of psoriasis and colitis. Across the tested disease settings, the authors observed greater therapeutic benefit than with the comparison approaches used in their experiments, including in atherosclerosis models.
These findings suggest that the antibody component can provide spatial control over where IL-2 activity is delivered, while the cytokine component continues to signal through its normal biological pathway. That combination could be useful for cytokine therapies in which activity must be directed toward diseased tissue rather than applied broadly.
Evidence stage and significance
The results support OSE targeting as a possible platform for directing immune-modulating treatments to inflamed tissue. They also provide a rationale for developing IL-2 therapies that improve tissue targeting without relying solely on mutations intended to change receptor selectivity.
The evidence is currently preclinical and comes from laboratory and in vivo models. Whether IL-2IT can achieve a similar balance of tissue targeting, Treg activity and therapeutic benefit in people will require clinical development. The preprint reports no human treatment results or regulatory approval.
Several authors are inventors on patents covering IL-2IT and related IL-2 constructs, and some hold interests in ILTOO Pharma, which is listed among the authors’ affiliations. The work is therefore an early, company-linked research report available as a bioRxiv preprint.