Dosing extracellular vesicles

Gupta, Dhanu; Zickler, Antje Maria; Andaloussi, Samir El

doi:10.1016/j.addr.2021.113961

Cited by 209 publications

(143 citation statements)

References 153 publications

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“…These findings imply that EV's aggregation may increase not only their half-life in circulation, as mentioned above, but also the amount of vesicles targeting desired cell population (Figures 1, 2). The latter fits in with the consideration of the optimal EV's dosing at a single cell scale and at the body scale (Gupta et al, 2021). Proposed by us EV's aggregation with antigen-specific antibodies takes an advantage over the latex beads, since antibodies could be safely degraded intracellularly, could limit the unwanted clearance of EVs by phagocytes, and may increase the specificity of cell targeting (Nazimek et al, 2021).…”

Section: Antigen-specific Antibodies and Light Chains In The Fight To Enhance Extracellular Vesicles Therapeutic Efficacymentioning

confidence: 82%

“…But very likely these choices would vary across the specific clinical indications or even patients. The current state-of-the-art technologies and methodologies have been widely summarized elsewhere ( Akuma et al, 2019 ; Doyle and Wang, 2019 ; Li et al, 2019 ; Gowen et al, 2020 ; Klyachko et al, 2020 ; Gupta et al, 2021 ; Johnson et al, 2021 ). However, the use of EV-based therapeutics requires still a very flexible approach for optimization, as it is built on the basis of constantly growing knowledge and clinical evidences.…”

Section: Challenges In Therapeutic Application Of Extracellular Vesiclesmentioning

confidence: 99%

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

Nazimek

Bryniarski

2021

Front. Cell Dev. Biol.

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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.

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Section: Antigen-specific Antibodies and Light Chains In The Fight To Enhance Extracellular Vesicles Therapeutic Efficacymentioning

confidence: 82%

Section: Challenges In Therapeutic Application Of Extracellular Vesiclesmentioning

confidence: 99%

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

Nazimek

Bryniarski

2021

Front. Cell Dev. Biol.

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“…In addition, the definition of the bioactive substance(s) will remain a critical precondition before the fundamental study and clinical application of Ti‐EVs (Willis et al., 2017 ). Evaluation of Ti‐EVs’ potency would be an excellent procedure in addressing the challenges of the inconsistencies in preparations and batch‐to‐batch variations (Gupta et al., 2021 ). Thus, a fit‐for‐purpose exosome potency unit (EPU) could be applied to purify bioactive EVs and standardize dosage among different EV preparations (Willis et al., 2017 ).…”

Section: Problems and Solutionsmentioning

confidence: 99%

Tissue‐derived extracellular vesicles in cancers and non‐cancer diseases: Present and future

Man

Gao

et al. 2021

J of Extracellular Vesicle

124

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Extracellular vesicles (EVs) are lipid‐bilayer membrane structures secreted by most cell types. EVs act as messengers via the horizontal transfer of lipids, proteins, and nucleic acids, and influence various pathophysiological processes in both parent and recipient cells. Compared to EVs obtained from body fluids or cell culture supernatants, EVs isolated directly from tissues possess a number of advantages, including tissue specificity, accurate reflection of tissue microenvironment, etc., thus, attention should be paid to tissue‐derived EVs (Ti‐EVs). Ti‐EVs are present in the interstitium of tissues and play pivotal roles in intercellular communication. Moreover, Ti‐EVs provide an excellent snapshot of interactions among various cell types with a common histological background. Thus, Ti‐EVs may be used to gain insights into the development and progression of diseases. To date, extensive investigations have focused on the role of body fluid‐derived EVs or cell culture‐derived EVs; however, the number of studies on Ti‐EVs remains insufficient. Herein, we summarize the latest advances in Ti‐EVs for cancers and non‐cancer diseases. We propose the future application of Ti‐EVs in basic research and clinical practice. Workflows for Ti‐EV isolation and characterization between cancers and non‐cancer diseases are reviewed and compared. Moreover, we discuss current issues associated with Ti‐EVs and provide potential directions.

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“…On top of that, the EV dose depends on the applied EV isolation and quantification method which enhances variation due to the wealth of available techniques. A meta-analysis of 64 preclinical studies revealed large variations in the applied EV dose and treatment regimen [ 188 ], highlighting another hurdle affecting comparison between studies and interpretation of the therapeutic capacity of the investigated EVs. Additionally, further research will be required to allow extrapolation of dosing and administration from preclinical models to humans [ 188 ].…”

Section: Practical Considerations Towards Evs As a Therapeutic Delivery Platform To The Brainmentioning

confidence: 99%

“…A meta-analysis of 64 preclinical studies revealed large variations in the applied EV dose and treatment regimen [ 188 ], highlighting another hurdle affecting comparison between studies and interpretation of the therapeutic capacity of the investigated EVs. Additionally, further research will be required to allow extrapolation of dosing and administration from preclinical models to humans [ 188 ]. A general notion that can be observed independent of the EV administration and dosing regimen is the limited EV circulation time whereby the majority of the EVs accumulate in the liver, lungs, kidneys and spleen [ 128 ].…”

Section: Practical Considerations Towards Evs As a Therapeutic Delivery Platform To The Brainmentioning

confidence: 99%

Special delEVery: Extracellular Vesicles as Promising Delivery Platform to the Brain

2021

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The treatment of central nervous system (CNS) pathologies is severely hampered by the presence of tightly regulated CNS barriers that restrict drug delivery to the brain. An increasing amount of data suggests that extracellular vesicles (EVs), i.e., membrane derived vesicles that inherently protect and transfer biological cargoes between cells, naturally cross the CNS barriers. Moreover, EVs can be engineered with targeting ligands to obtain enriched tissue targeting and delivery capacities. In this review, we provide a detailed overview of the literature describing a natural and engineered CNS targeting and therapeutic efficiency of different cell type derived EVs. Hereby, we specifically focus on peripheral administration routes in a broad range of CNS diseases. Furthermore, we underline the potential of research aimed at elucidating the vesicular transport mechanisms across the different CNS barriers. Finally, we elaborate on the practical considerations towards the application of EVs as a brain drug delivery system.

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Dosing extracellular vesicles

Cited by 209 publications

References 153 publications

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

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

Tissue‐derived extracellular vesicles in cancers and non‐cancer diseases: Present and future

Special delEVery: Extracellular Vesicles as Promising Delivery Platform to the Brain

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