Exosome-SIRPα, a CD47 blockade increases cancer cell phagocytosis

Koh, Eunee; Lee, Eun Jung; Nam, Gi Hoon; Hong, Yun Sik; Cho, Eunji; Yang, Yoosoo; Kim, In‐San

doi:10.1016/j.biomaterials.2017.01.004

Cited by 284 publications

(223 citation statements)

References 34 publications

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“…To address these issues, an exosome-based platform was developed to provide high avidity to CD47. SIRPα-exosomes were found to highly antagonize the “don’t eat me” signal of CD47 on cancer cells, thereby enhancing the phagocytosis of tumour cells by bone-marrow derived macrophages in vitro and suppressing tumour growth in xenografts [121]. Remarkably, the therapeutic index of this exosome-mediated CD47 blockade against tumour growth was higher than that of the same dose of monomeric SIRPα.…”

Section: Therapeutic Applications Of Surface-modified Evsmentioning

confidence: 99%

“…Remarkably, the therapeutic index of this exosome-mediated CD47 blockade against tumour growth was higher than that of the same dose of monomeric SIRPα. Given that native SIRPα proteins form and work as homodimers when they bind with CD47, the membrane scaffold offered by naturally derived exosomes could facilitate the formation of membrane-spanning SIRPα clusters, augmenting their effect against CD47 [121]. …”

Section: Therapeutic Applications Of Surface-modified Evsmentioning

confidence: 99%

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Extracellular vesicles as a platform for membrane‐associated therapeutic protein delivery

Yang

Hong

Cho

et al. 2018

J of Extracellular Vesicle

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186

148

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Membrane proteins are of great research interest, particularly because they are rich in targets for therapeutic application. The suitability of various membrane proteins as targets for therapeutic formulations, such as drugs or antibodies, has been studied in preclinical and clinical studies. For therapeutic application, however, a protein must be expressed and purified in as close to its native conformation as possible. This has proven difficult for membrane proteins, as their native conformation requires the association with an appropriate cellular membrane. One solution to this problem is to use extracellular vesicles as a display platform. Exosomes and microvesicles are membranous extracellular vesicles that are released from most cells. Their membranes may provide a favourable microenvironment for membrane proteins to take on their proper conformation, activity, and membrane distribution; moreover, membrane proteins can cluster into microdomains on the surface of extracellular vesicles following their biogenesis. In this review, we survey the state-of-the-art of extracellular vesicle (exosome and small-sized microvesicle)-based therapeutics, evaluate the current biological understanding of these formulations, and forecast the technical advances that will be needed to continue driving the development of membrane protein therapeutics.

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Section: Therapeutic Applications Of Surface-modified Evsmentioning

confidence: 99%

Section: Therapeutic Applications Of Surface-modified Evsmentioning

confidence: 99%

Extracellular vesicles as a platform for membrane‐associated therapeutic protein delivery

Yang

Hong

Cho

et al. 2018

J of Extracellular Vesicle

Self Cite

186

148

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show abstract

“…Furthermore, several reports indicate that EVs may improve pharmacokinetics and preserve activity of incorporated therapeutics. Furthermore, EVs have low immunogenicity due to the expression of CD47 receptor that interacts with signal regulatory protein α (SIRPα) to produce a “don't eat me” signal in phagocytes . Finally, EVs can exert unique biological activity reflective of their origin.…”

Section: Introductionmentioning

confidence: 99%

TPP1 Delivery to Lysosomes with Extracellular Vesicles and their Enhanced Brain Distribution in the Animal Model of Batten Disease

Haney

Klyachko

Harrison

et al. 2019

Adv Healthcare Materials

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Extracellular vesicles (EVs) are promising natural nanocarriers for delivery of various types of therapeutics. Earlier engineered EV‐based formulations for neurodegenerative diseases and cancer are reported. Herein, the use of macrophage‐derived EVs for brain delivery of a soluble lysosomal enzyme tripeptidyl peptidase‐1, TPP1, to treat a lysosomal storage disorder, Neuronal Ceroid Lipofuscinoses 2 (CLN2) or Batten disease, is investigated. TPP1 is loaded into EVs using two methods: i) transfection of parental EV‐producing macrophages with TPP1‐encoding plasmid DNA (pDNA) or ii) incorporation therapeutic protein TPP1 into naive empty EVs. For the former approach, EVs released by pretransfected macrophages contain the active enzyme and TPP1‐encoding pDNA. To achieve high loading efficiency by the latter approach, sonication or permeabilization of EV membranes with saponin is utilized. Both methods provide proficient incorporation of functional TPP1 into EVs (EV‐TPP1). EVs significantly increase stability of TPP1 against protease degradation and provide efficient TPP1 delivery to target cells in in vitro model of CLN2. The majority of EV‐TPP1 (≈70%) is delivered to target organelles, lysosomes. Finally, a robust brain accumulation of EV carriers and increased lifespan is recorded in late‐infantile neuronal ceroid lipofuscinosis (LINCL) mouse model following intraperitoneal administration of EV‐TPP1.

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“…Overall, exosomes are cleared by phagocytic cells particularly in the liver and spleen reflecting relatively short circulating half‐life. Recently, it was reported that SIRPα could make exosomes able to escape from macrophages and lead to enhancement of retention in the circulation . On the other hand, the appropriate size of exosomes (100 nm) can be facilitated homing them in tumor tissues through the enhanced permeation and retention effect .…”

Section: Therapeutic Role Of Exosomes In Cancermentioning

confidence: 99%

“…Recently, it was reported that SIRPα could make exosomes able to escape from macrophages and lead to enhancement of retention in the circulation. 203 On the other hand, the appropriate size of exosomes (100 nm) can be facilitated homing them in tumor tissues through the enhanced permeation and retention effect. 240,241 PEGylation of exosome increases their biostability and circulation time.…”

Section: Potential and Challenges Of Exosomes As A Nanodrug Delivermentioning

confidence: 99%

Exosomes and cancer: From oncogenic roles to therapeutic applications

et al. 2019

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Exosomes belong to extracellular vehicles that were produced and secreted from most eukaryotic cells and are involved in cell‐to‐cell communications. They are an effective delivery system for biological compounds such as mRNAs, microRNAs (miRNAs), proteins, lipids, saccharides, and other physiological compounds to target cells. In this way, they could influence on cellular pathways and mediate their physiological behaviors including cell proliferation, tumorigenesis, differentiation, and so on. Many research studies focused on their role in cancers and also on potentially therapeutic and biomarker applications. In the current study, we reviewed the exosomes' effects on cancer progression based on their cargoes including miRNAs, long noncoding RNAs, circular RNAs, DNAs, mRNAs, proteins, and lipids. Moreover, their therapeutic roles in cancer were considered. In this regard, we have given a brief overview of challenges and obstacles in using exosomes as therapeutic agents.

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Exosome-SIRPα, a CD47 blockade increases cancer cell phagocytosis

Cited by 284 publications

References 34 publications

Extracellular vesicles as a platform for membrane‐associated therapeutic protein delivery

Extracellular vesicles as a platform for membrane‐associated therapeutic protein delivery

TPP1 Delivery to Lysosomes with Extracellular Vesicles and their Enhanced Brain Distribution in the Animal Model of Batten Disease

Exosomes and cancer: From oncogenic roles to therapeutic applications

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