Comprehensive toxicity and immunogenicity studies reveal minimal effects in mice following sustained dosing of extracellular vesicles derived from HEK293T cells

Extracellular vesicles (EVs) are under evaluation as therapeutics or as vehicles for drug delivery. Preclinical studies of EVs often use mice or other animal models to assess efficacy and disposition. However, as most EVs under evaluation are derived from human cells, they may elicit immune response...

Full description

Saved in:
Bibliographic Details
Published in:Journal of extracellular vesicles 2017-12, Vol.6 (1), p.1324730-n/a
Main Authors: Zhu, Xiaohua, Badawi, Mohamed, Pomeroy, Steven, Sutaria, Dhruvitkumar S., Xie, Zhiliang, Baek, Alice, Jiang, Jinmai, Elgamal, Ola A., Mo, Xiaokui, Perle, Krista La, Chalmers, Jeffrey, Schmittgen, Thomas D., Phelps, Mitch A.
Format: Article
Language:English
Subjects:
Alzheimer's disease
Animal models
Animals
C57BL/6
Cell culture
Cells
cytokines
drug carriers
Drug delivery
Drug dosages
Exosomes
Extracellular vesicles
Gene expression
Genetic engineering
Hematology
Hepatitis
Immune clearance
Immune response
Immunogenicity
Immunology
immunophenotyping
Liver cancer
MicroRNAs
miR-199a-3p
Necropsy
Peptides
Proteins
Rodents
Spleen
Studies
Toxicity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Extracellular vesicles (EVs) are under evaluation as therapeutics or as vehicles for drug delivery. Preclinical studies of EVs often use mice or other animal models to assess efficacy and disposition. However, as most EVs under evaluation are derived from human cells, they may elicit immune responses which may contribute to toxicities or enhanced EV clearance. Furthermore, EVs from different cell sources or EVs comprising various cargo may differ with respect to immunogenicity or toxicity. To assess EV-induced immune response and toxicity, we dosed C57BL/6 mice with EVs intravenously and intraperitoneally for 3 weeks. EVs were harvested from wild type or engineered HEK293T cells which were modified to produce EVs loaded with miR-199a-3p and chimeric proteins. Blood was collected to assess hematology, blood chemistry, and immune markers. Spleen cells were immunophenotyped, and tissues were harvested for gross necropsy and histopathological examination. No signs of toxicity were observed, and minimal evidence of changes in immune markers were noted in mice dosed with engineered, but not with wild type EVs. This study provides a framework for assessment of immunogenicity and toxicity that will be required as EVs from varying cell sources are tested within numerous animal models and eventually in humans.
ISSN:2001-3078
2001-3078
DOI:10.1080/20013078.2017.1324730