Increasing the Therapeutic Efficacy of Extracellular Vesicles From the Antigen-Specific Antibody and Light Chain Perspective

Abstract

Due to their exceptional properties, extracellular vesicles (EVs) receive special attention as next generation biotherapeutics and vehicles for drug delivery. However, despite having many advantages over cell-based therapies, EVs usually exert lower therapeutic efficacy. This results from a number of hurdles that are faced by the EV-based approaches. Administered EVs could be rapidly cleared by the mononuclear phagocytes as well as can randomly distribute within various tissues, making tissue penetration and cell targeting insufficient. However, recent research findings imply that these limitations could be overcome with the use of antigen-specific antibodies and light chains. Major histocompatibility complex (MHC) class II-expressing EVs have been shown to form aggregates after co-incubation with antigen-specific antibodies, which greatly enhanced their biological efficacy. On the other hand, EVs could be coated with antibody light chains of chosen specificity to direct them towards desired target cell population. Both findings open up a promising perspective to achieve the highest efficacy of the EV-based approaches. Herein we discuss the opportunities for enhancing extracellular vesicle’s biological activity by using specific antibodies and light chains in the context of the challenges faced by such therapeutic approach.

Biodelivery of therapeutic extracellular vesicles: should mononuclear phagocytes always be feared?

“…EVs are considered key candidates for cell-free therapies, including allergy and autoimmunity treatment ( Nazimek and Bryniarski, 2020a ; Nazimek and Bryniarski, 2021 ). However, EV therapeutic efficacy is affected by limited bioavailability due to their rapid clearance by MPS cells.…”

Extracellular Vesicles—Oral Therapeutics of the Future

“…Our recent studies revealed the mechanism of antigen-specific immune tolerance in mice, which is mediated by suppressor T cells [ 101 ] that act through the release of EVs carrying immune regulatory miRNA-150 [ 102 , 103 ]. The specificity of EVs’ action is ensured by the surface coating of antibody light chains [ 104 ], which also support cell targeting by EVs [ 105 ]. As a result, EV-targeted antigen-presenting cells, including macrophages [ 106 ], induce immune tolerance to self-antigens and contact allergens [ 107 ].…”

Engineered Exosome for Drug Delivery: Recent Development and Clinical Applications

“…This method has several advantages, such as high drug-loading efficiency, low toxicity, strong controllability, and low cost. 50–52 Co-incubation allows exosomes to protect and transport drugs to target cells stably and has better biocompatibility in the human body than traditional synthetic nanoparticles. Co-incubation also enables adjusting the surface proteins and contents of exosomes by changing the co-incubation conditions.…”