Incubating EVs with antigen-specific IgG antibodies leads to their aggregation, which enhances their biological efficacy by increasing the amount of EVs that target desired cell population, and by lowering the risk of urinary excretion. towards desired target cell population. Both findings open up a promising perspective to achieve the Tirbanibulin Mesylate highest efficacy of the EV-based approaches. Herein we discuss the opportunities for enhancing extracellular vesicles biological activity by using specific antibodies and light chains in the context of the challenges faced by such therapeutic approach. Keywords:antibody, biotherapeutics, exosomes, extracellular vesicles, treatment efficiency == Introduction == Extracellular vesicles (EVs) encompass all classes of lipid-membrane vesicles that differ in the formation pathway but are then released by virtually all cells to their surrounding microenvironment (Yez-M et al., 2015;Pironti et al., 2021). As a newly discovered mood of intercellular communication, they currently receive special attention as next generation biotherapeutics with likely very limited adverse Tirbanibulin Mesylate effects of administration (Kalluri and LeBleu, 2020), and multiple advantages over synthetic liposomes (Vader et al., 2016;Nazimek and Bryniarski, 2020b). Accordingly, EVs, exosomes Rabbit Polyclonal to p47 phox especially, are considered promising vehicles for drug delivery due to their biocompatibility and exceptional stability in biological fluids (Akuma et al., 2019). In this aspect, however, it should be stressed that EVs themselves are very complex and thus their components should be taken into consideration as additional active drug constituents (Lener et al., 2015). Furthermore, EVs could be used by pathogens for infection spreading, and thus one can speculate that they may transfer virulence factors, which has to be taken into consideration while manipulating EVs for therapeutic applications (Pironti et al., 2021). On the other hand, attempts to solve the challenges of stem cell therapy allowed to discover that EVs are the main paracrine factors that actually mediate the effects induced by administration of their parental cells (Johnson et al., 2021;Wang et al., 2021). However, despite having many advantages over such approaches, EV-based therapeutics usually achieve lower or almost the same therapeutic efficacy than releasing cells (Kalluri and LeBleu, 2020). Our current research findings suggest that some of these limitations could be overcome by aggregating EVs with antigen-specific antibodies and by increasing the specificity of cell targeting with antibody light chains (LCs). As discussed below, such approaches offer a promising perspective in enhancing EVs therapeutic activity (Figure 1). == FIGURE 1. == Postulated advantages of extracellular vesicle (EV) aggregation with antigen-specific antibodies and coating with antigen-specific light chains (LC). After systemic administration, therapeutic EVs disperse and mix with their counterparts in the circulation, from which they pass into the tissues. However, their tissue distribution is at least partly random with the preferential accumulation in mononuclear phagocyte-enriched organs, such as liver, spleen, and lungs, where they are rapidly cleared by macrophages. In addition, injected EVs could likely be excreted in urine due to their putative ability to penetrate kidneys glomerular filtration barrier. Altogether, these hurdles make desired tissue Tirbanibulin Mesylate penetration and cell targeting insufficient to induce the expected therapeutic effect. However, recent research findings showed that these limitations could be overcome with the use of antigen-specific antibodies and light chains. Incubating EVs with antigen-specific IgG antibodies leads to their aggregation, which enhances their biological efficacy by increasing the amount of EVs that target desired cell population, and by lowering the risk of urinary excretion. In addition, coating EVs with antigen-specific LCs directs them towards target cells, Tirbanibulin Mesylate which augments the selectivity of tissue targeting, and limits the unwanted clearance by phagocytes. == Poor is the Pupil Who Does not Surpass his Master1 == Recent studies and clinical trials uncovered a number of hurdles that are faced by the cell-based therapies. The widely described obstacles affecting the efficacy of stem cell therapies result mainly from a lack of standardized treatment methods, low percentage of cells that reach the desired tissue/organ, the poor survival of engrafted cells that often rapidly undergo apoptosis in targeted cells, and finally from your diversity of yielded cell populations between individual Tirbanibulin Mesylate donors (Hassanzadeh et al., 2021;Johnson et al., 2021;Wang et al., 2021). In addition, stem cell treatments raise issues about possible adverse events of the treatment that are associated with the risk of tumorigenesis, the possibility of disrupted or irregular maturation of infused cells as well as with their eventual differentiation in undesirable cells (Lukomska et al., 2019). On the other hand, the main obstacle related to.