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Extracellular Vesicles: A New Mechanism of Intercellular Communication for Immune...
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Extracellular Vesicles: A New Mechanism of Intercellular Communication for Immune Regulation in Cancer, Autoimmune Diseases, and Infectious Diseases

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Cellular/Molecular Immunology".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 8700

Special Issue Editor

Dr. Masamitsu Kanada

E-Mail Website
Guest Editor
Institute for Quantitative Health Science and Engineering, Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI, USA
Interests: cancer; regenerative medicine; eye disease; gene therapy; drug delivery; genome editing; molecular imaging; Biochemistry; neurodegeneration

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs), released by eukaryotes, archaea, and bacteria, are universal and evolutionally conserved mechanisms for intercellular communication. EVs carry various active biomolecules, such as DNA, RNA, proteins, and lipids, and deliver them to adjacent and distant cells in the body. Previous studies have demonstrated intercellular communication between the immune system and interacting cells via EVs. Recent studies have further developed engineered EVs to modulate the immune system. EVs can be found in the blood as well. Therefore, the assessment of circulating EVs is an active area of research for identifying reliable biomarkers of disease progression and therapy response. Imaging techniques to monitor the efficiency of immune-modulatory or therapeutic EVs are also being developed. Despite the exciting potential of EVs as clinical therapeutics, however, additional work is needed to fully characterize their biodistribution and pharmacokinetics, as well as reproducible EV production. In this Special Issue, we will cover some of the new insights in EV-mediated immune regulation and advances in the field to increase the potential of engineered EVs for therapy and diagnosis in cancer, autoimmune diseases, and infectious diseases.

Dr. Masamitsu Kanada
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • extracellular vesicles (EVs)
  • exosomes
  • microvesicles
  • cancer
  • immunization vaccines
  • infectious diseases
  • imaging

Published Papers (4 papers)

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Research

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15 pages, 9874 KiB  
Article
Phosphatidylserine-Exposing Annexin A1-Positive Extracellular Vesicles: Potential Cancer Biomarkers
by Gloria I. Perez, Matthew P. Bernard, Daniel Vocelle, Ahmed A. Zarea, Najla A. Saleh, Matthew A. Gagea, Doug Schneider, Maxine Bauzon, Terry Hermiston and Masamitsu Kanada
Vaccines 2023, 11(3), 639; https://doi.org/10.3390/vaccines11030639 - 13 Mar 2023
Cited by 3 | Viewed by 1902
Abstract
Under physiological conditions, phosphatidylserine (PS) predominantly localizes to the cytosolic leaflet of the plasma membrane of cells. During apoptosis, PS is exposed on the cell surface and serves as an “eat-me” signal for macrophages to prevent releasing self-immunogenic cellular components from dying cells [...] Read more.
Under physiological conditions, phosphatidylserine (PS) predominantly localizes to the cytosolic leaflet of the plasma membrane of cells. During apoptosis, PS is exposed on the cell surface and serves as an “eat-me” signal for macrophages to prevent releasing self-immunogenic cellular components from dying cells which could potentially lead to autoimmunity. However, increasing evidence indicates that viable cells can also expose PS on their surface. Interestingly, tumor cell-derived extracellular vesicles (EVs) externalize PS. Recent studies have proposed PS-exposing EVs as a potential biomarker for the early detection of cancer and other diseases. However, there are confounding results regarding subtypes of PS-positive EVs, and knowledge of PS exposure on the EV surface requires further elucidation. In this study, we enriched small EVs (sEVs) and medium/large EVs (m/lEVs) from conditioned media of breast cancer cells (MDA-MB-231, MDA-MB-468) and non-cancerous cells (keratinocytes, fibroblasts). Since several PS-binding molecules are available to date, we compared recombinant proteins of annexin A5 and the carboxylated glutamic acid domain of Protein S (GlaS), also specific for PS, to detect PS-exposing EVs. Firstly, PS externalization in each EV fraction was analyzed using a bead-based EV assay, which combines EV capture using microbeads and analysis of PS-exposing EVs by flow cytometry. The bulk EV assay showed higher PS externalization in m/lEVs derived from MDA-MB-468 cells but not from MDA-MB-231 cells, while higher binding of GlaS was also observed in m/lEVs from fibroblasts. Second, using single EV flow cytometry, PS externalization was also analyzed on individual sEVs and m/lEVs. Significantly higher PS externalization was detected in m/lEVs (annexin A1+) derived from cancer cells compared to m/lEVs (annexin A1+) from non-cancerous cells. These results emphasize the significance of PS-exposing m/lEVs (annexin A1+) as an undervalued EV subtype for early cancer detection and provide a better understanding of PS externalization in disease-associated EV subtypes. Full article
(This article belongs to the Special Issue Extracellular Vesicles: A New Mechanism of Intercellular Communication for Immune Regulation in Cancer, Autoimmune Diseases, and Infectious Diseases)
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19 pages, 3473 KiB  
Article
Development of a Bispecific Nanobody Targeting CD20 on B-Cell Lymphoma Cells and CD3 on T Cells
by Yanlong Liu, Kexin Ao, Fuxiang Bao, Yi Cheng, Yanxia Hao, Huimin Zhang, Shan Fu, Jiaqi Xu and Qiyao Wu
Vaccines 2022, 10(8), 1335; https://doi.org/10.3390/vaccines10081335 - 17 Aug 2022
Cited by 3 | Viewed by 2582
Abstract
B-cell lymphoma is a group of malignant proliferative diseases originating from lymphoid tissue with different clinical manifestations and biological characteristics. It can occur in any part of the body, accounting for more than 80% of all lymphomas. The present study aimed to construct [...] Read more.
B-cell lymphoma is a group of malignant proliferative diseases originating from lymphoid tissue with different clinical manifestations and biological characteristics. It can occur in any part of the body, accounting for more than 80% of all lymphomas. The present study aimed to construct bispecific single-domain antibodies against CD20 and CD3 and to evaluate their function in killing tumor cells in vitro. A Bactrian camel was immunized with a human CD20 extracellular peptide, and the VHH gene was cloned and ligated into a phagemid vector to construct the phage antibody display library. A phage antibody library with a size of 1.2 × 108 was successfully constructed, and the VHH gene insertion rate was 91.7%. Ninety-two individual clones were randomly picked and screened by phage ELISA. Six strains with the high binding ability to human CD20 were named 11, 30, 71, 72, 83, and 92, and induced expression and purification were performed to obtain soluble CD20 single-domain antibodies. The obtained single-domain antibodies could specifically bind to human CD20 polypeptide and cell surface-expressed CD20 molecules in ELISA, Western blot, and cell immunofluorescence assays. The anti-CD20/CD3 bispecific nanobody (BsNb) was successfully constructed by fusing the anti-CD20 VHH gene with the anti-CD3 VHH and the bispecific single-domain antibody was expressed, purified, and validated. Anti-CD20/CD3 BsNb can specifically bind CD20 molecules on the surface of human lymphoma Raji cells and CD3 molecules on the surface of T cells in flow cytometry analysis and effectively mediate peripheral blood mononuclear cells (PBMCs) target Raji cells with a killing efficiency of up to 30.4%, as measured by the lactate dehydrogenase (LDH) method. The release of hIFN-γ from PBMCs during incubation with anti-CD20/CD3 BsNb was significantly higher than that of the control group (p < 0.01). The anti-CD20/CD3 BsNb could maintain 80% binding activity after incubation with human serum at 37 °C for 48 h. These results indicated the strong antitumor effect of the constructed anti-CD20/CD3 BsNb and laid the foundation for the further development of antitumor agents and the clinical application of anti-CD20/CD3 BsNb. Full article
(This article belongs to the Special Issue Extracellular Vesicles: A New Mechanism of Intercellular Communication for Immune Regulation in Cancer, Autoimmune Diseases, and Infectious Diseases)
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Review

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20 pages, 1137 KiB  
Review
Trick-or-Trap: Extracellular Vesicles and Viral Transmission
by Juan-Vicente Bou, Shuhei Taguwa and Yoshiharu Matsuura
Vaccines 2023, 11(10), 1532; https://doi.org/10.3390/vaccines11101532 - 27 Sep 2023
Viewed by 1014
Abstract
Extracellular vesicles (EVs) are lipid membrane-enclosed particles produced by most cells, playing important roles in various biological processes. They have been shown to be involved in antiviral mechanisms such as transporting antiviral molecules, transmitting viral resistance, and participating in antigen presentation. While viral [...] Read more.
Extracellular vesicles (EVs) are lipid membrane-enclosed particles produced by most cells, playing important roles in various biological processes. They have been shown to be involved in antiviral mechanisms such as transporting antiviral molecules, transmitting viral resistance, and participating in antigen presentation. While viral transmission was traditionally thought to occur through independent viral particles, the process of viral infection is complex, with multiple barriers and challenges that viruses must overcome for successful infection. As a result, viruses exploit the intercellular communication pathways of EVs to facilitate cluster transmission, increasing their chances of infecting target cells. Viral vesicle transmission offers two significant advantages. Firstly, it enables the collective transmission of viral genomes, increasing the chances of infection and promoting interactions between viruses in subsequent generations. Secondly, the use of vesicles as vehicles for viral transmission provides protection to viral particles against environmental factors, while also expanding the cell tropism allowing viruses to reach cells in a receptor-independent manner. Understanding the role of EVs in viral transmission is crucial for comprehending virus evolution and developing innovative antiviral strategies, therapeutic interventions, and vaccine approaches. Full article
(This article belongs to the Special Issue Extracellular Vesicles: A New Mechanism of Intercellular Communication for Immune Regulation in Cancer, Autoimmune Diseases, and Infectious Diseases)
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13 pages, 1041 KiB  
Review
Exosomes as Rheumatoid Arthritis Diagnostic Biomarkers and Therapeutic Agents
by Romina Heydari, Fatemeh Koohi, Milad Rasouli, Kimia Rezaei, Elham Abbasgholinejad, Sander Bekeschus and Mohammad Doroudian
Vaccines 2023, 11(3), 687; https://doi.org/10.3390/vaccines11030687 - 17 Mar 2023
Cited by 15 | Viewed by 2619
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that causes systemic inflammation, autoimmunity, and joint abnormalities that result in permanent disability. Exosomes are nanosized extracellular particles found in mammals (40–100 nm). They are a transporter of lipids, proteins, and genetic material involved [...] Read more.
Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that causes systemic inflammation, autoimmunity, and joint abnormalities that result in permanent disability. Exosomes are nanosized extracellular particles found in mammals (40–100 nm). They are a transporter of lipids, proteins, and genetic material involved in mammalian cell–cell signaling, biological processes, and cell signaling. Exosomes have been identified as playing a role in rheumatoid arthritis-related joint inflammation (RA). Uniquely functioning extracellular vesicles (EVs) are responsible for the transport of autoantigens and mediators between distant cells. In addition, paracrine factors, such as exosomes, modulate the immunomodulatory function of mesenchymal stem cells (MSCs). In addition to transporting genetic information, exosomes convey miRNAs between cells and have been studied as drug delivery vehicles. In animal models, it has been observed that MSCs secrete EVs with immunomodulatory properties, and promising results have been observed in this area. By understanding the diversity of exosomal contents and their corresponding targets, it may be possible to diagnose autoimmune diseases. Exosomes can be employed as diagnostic biomarkers for immunological disorders. We here discuss the most recent findings regarding the diagnostic, prognostic, and therapeutic potential of these nanoparticles in rheumatoid arthritis and provide an overview of the evidence pertaining to the biology of exosomes in RA. Full article
(This article belongs to the Special Issue Extracellular Vesicles: A New Mechanism of Intercellular Communication for Immune Regulation in Cancer, Autoimmune Diseases, and Infectious Diseases)
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