Extracellular Vesical-based Cytokine Storm Therapy

The invention relates to the use of extracellular vesicles (EVs) loaded with CD24, a biological immunomodulator, for treating hypercytokinemia (also named cytokine storm, cytokine storm syndrome, or cytokine release syndrome). Hypercytokinemia can be caused by a number of infectious and non-infectious etiologies, especially viral respiratory infections such as H5N1 influenza, SARS-CoV-1, and SARS-CoV-2 (COVID-19 agent). Other causative agents include the Epstein-Barr virus, cytomegalovirus, and group A streptococcus, and non-infectious conditions such as graft-versus-host disease. The present disclosure relates to the application of EVs that are derived from any cells including human mesenchymal stem cells and are loaded with natural or engineered CD24 for therapeutic usages in human and animals.

Our invention allows one to load natural or engineered human or animal CD24 molecules into extracellular vesicles including exosomes without being cleaved or modified by extracellular enzymes, bound by host proteins, or neutralized by host immune responses. Prior to our invention, the N-terminal 56 amino acid residues of human CD24 has to been fused with the Fc region of human IgG1 (CD24Fc) before being used as a protein drug to treat hypercytokinemia.

The invention will allow a very high number of CD24 molecules to be loaded into extracellular vesicles, known as natural nanoparticles. The EVs loaded with CD24 can be directly used as therapeutic agents for treating hypercytokinemia or used in combination with other immuno modulators in order to achieve potential synergy.