Understanding the Mode of Action of a Micro-Immunotherapy Formulation: Pre-Clinical Evidence from the Study of 2LEBV? Active Ingredients

Background: Epstein-Barr virus (EBV) is often kept silent and asymptomatic; however, its reactivation induces a chronic and/or recurrent infection that is associated with numerous diseases, including cancer and inflammation-related disorders. As no specific treatment is currently available, the immune factors-based micro-immunotherapy (MI) medicine 2LEBV (R) could be considered a valuable therapeutic option to sustain the immune system in EBV reactivation. Methods: The present work aimed to investigate, for the first time, the effect of 2LEBV (R) in several in vitro models of uninfected immune-related cells. Results: 2LEBV (R) displayed phagocytosis-enhancing capabilities in granulocytes. In human peripheral blood mononuclear cells (PBMCs), it increased the intra- and extra-cellular expression of interleukin (IL)-2. Moreover, it modulated the secretion of other cytokines, increasing IL-4, IL-6, and tumor necrosis factor-alpha levels or lowering other cytokines levels such as IL-9. Finally, 2LEBV (R) reduced the expression of human leukocyte antigen (HLA)-II in endothelial cells and macrophages. Conclusions: Although these data are still preliminary and the chosen models do not consider the underlying EBV-reactivation mechanisms, they still provide a better understanding of the mechanisms of action of 2LEBV (R), both at functional and molecular levels. Furthermore, they open perspectives regarding the potential targets of 2LEBV (R) in its employment as a therapeutic intervention for EBV-associated diseases.