CD25 Targeted IL-2 Therapy for Respiratory Viral Infections

Abstract

Researchers at the University of Central Florida have developed a new approach for modulating the inflammatory response during acute respiratory viral infections. This approach generates a robust inflammatory response against the viral infection while minimizing damaging inflammation and immunopathology. Infections by respiratory viruses, such as influenza viruses and coronaviruses, may cause severe disease and may also lead to further complications such as the “cytokine storm.” This overactive immune response can cause tissue damage and organ failure. Hence, new treatments that can induce anti-inflammatory and pro-inflammatory responses during respiratory viral infections may significantly improve clinical outcomes.

Technical Details

This technology uses a combination of the cytokine interleukin-2 (IL-2) and a monoclonal antibody specific for IL-2 to form a complex (IL-2 antibody complex). The IL-2 antibody binds to the IL-2 in a manner that sterically inhibits binding to the beta chain of the IL-2 receptor (CD122). The IL-2 antibody complex specifically targets the IL-2 to subsets of cells that express the alpha chain of the IL-2 receptor (CD25). This CD25 targeted IL-2 approach is based on the researchers’ findings that treatment with the IL-2 antibody complex (using anti-mouse IL-2 monoclonal antibody clone JES6-1A12) promoted a strong inflammatory response while reducing lung immunopathology in mice infected with the Influenza A virus (IAV). The treatment induced simultaneous engagement of diverse lymphocyte populations: 1) antiviral T-cells, 2) regulatory CD4 T-cells, and 3) innate lymphoid cells (involved in tissue repair processes).

There were notable histological differences in the lungs of IAV-infected mice treated with the IL-2 antibody complex compared to IAV-infected untreated mice. While treatment with the IL-2 antibody complex promoted a strong acute inflammatory response during viral infection, mice treated with the complex displayed reduced bronchial inflammation (which was virtually absent) compared to untreated mice. Additionally, treatment with the IL-2 antibody complex promoted the formation of memory CD4 T-cells following infection. This targeted IL-2 based approach may simultaneously enhance antiviral immune responses, protect against tissue damage, and boost pathogen-specific T-cell memory formation.

Partnering Opportunity

The research team is seeking partners for licensing and/or research collaboration.

Stage of Development

Mouse Influenza A virus infection model.

Benefit

Market Application

Publications

CD25-Targeted IL-2 Signals Promote Improved Outcomes of Influenza Infection and Boost Memory CD4 T Cell Formation, The Journal of Immunology,  June 15, 2020, 204 (12) 3307-3314; DOI: https://doi.org/10.4049/jimmunol.2000205