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Exosome vaccine

Sabari Nath Neerukonda, Phaedra Tavlarides-Hontz, Fiona McCarthy, Kenneth Pendarvis, Mark S Parcells
Marek's disease virus (MDV) is the causative agent of Marek's disease (MD), a complex pathology of chickens characterized by paralysis, immunosuppression, and T-cell lymphomagenesis. MD is controlled in poultry production via vaccines administered in ovo or at hatch, and these confer protection against lymphoma formation, but not superinfection by MDV field strains. Despite vaccine-induced humoral and cell-mediated immune responses, mechanisms eliciting systemic protection remain unclear. Here we report the contents of serum exosomes to assess their possible roles as indicators of systemic immunity, and alternatively, tumor formation...
February 5, 2019: Genes
Bruno Deltreggia Benites, Adriana da Silva Santos Duarte, Ana Leda Figueiredo Longhini, Irene Santos, Marisa Claudia Alvarez, Ligia Nunes de Morais Ribeiro, Eneida de Paula, Sara Teresinha Olalla Saad
Exosomes may represent an interesting antigenic pulse for new forms of anti-tumor immunotherapy. We evaluated exosomes from serum of patients with acute myeloid leukemia (AML) as an antigenic source for dendritic cells (DC) and the effects upon antitumor cytotoxicity, assessed by the percentage of specific lysis of K562 leukemic cells in co-cultures. Surprisingly, incubation of exosomes with DCs decreased lysis of K562, which may correspond to a mechanism of tumor evasion in vivo. However, when immature DCs were pulsed with exosomes purified from K562 culture supernatants, the lysis of target cells was notably enhanced, associated with a substantial increase in the expression of the maturation marker CD83...
February 9, 2019: Vaccine
Kavitha Yaddanapudi, Shuhan Meng, Aaron G Whitt, Numan Al Rayyan, Jamaal Richie, Allison Tu, John W Eaton, Chi Li
The antigenic similarity between embryos and tumors has raised the idea of using embryonic material as a preventative vaccine against neoplastic disease. Indeed, we have previously reported that a vaccine comprises allogeneic murine embryonic stem cells (ESCs) and murine fibroblasts expressing GM-CSF (to amplify immune responses) successfully blocks the outgrowth of an implantable cancer (Lewis lung carcinoma; LLC) and lung tumors generated in mice using a combination of a mutagen followed by chronic pulmonary inflammation...
2019: Oncoimmunology
Diego de Souza Gonçalves, Marina da Silva Ferreira, Allan J Guimarães
Extracellular vesicles (EVs) are membranous compartments of distinct cellular origin and biogenesis, displaying different sizes and include exosomes, microvesicles, and apoptotic bodies. The EVs have been described in almost every living organism, from simple unicellular to higher evolutionary scale multicellular organisms, such as mammals. Several functions have been attributed to these structures, including roles in energy acquisition, cell-to-cell communication, gene expression modulation and pathogenesis...
February 1, 2019: Bioengineering
Germano Castelli, Federica Bruno, Laura Saieva, Riccardo Alessandro, Luca Galluzzi, Aurora Diotallevi, Fabrizio Vitale
In recent years, several studies demonstrated the role of exosomes in intercellular communications, several Leishmania species belonging to subgenera Leishmania and Viannia have been demonstrated to release exosomes, and their role in parasite-macrophage interactions and in leishmaniasis development has been investigated. However, the release of exosomes by Leishmania infantum has not been studied so far. The aim of this study was to isolate and characterize L. infantum exosomes, and to investigate the biological activity of these exosomes in macrophage cultures...
February 1, 2019: Experimental Parasitology
Paola Di Bonito, Luisa Accardi, Luisa Galati, Flavia Ferrantelli, Maurizio Federico
Some human papillomavirus (HPV) genotypes are universally recognized as major etiological agents not only of ano-genital tumors but also of head and neck cancers, which show increasing incidence. The evaluation of current and future therapeutic approaches against HPV-induced tumors is a global health priority, despite an effective prophylactic vaccine against 7 of the 12 genotypes involved in the etiology of tumors being currently available. In this review, we present the main anti-HPV therapeutic approaches in clinical experimentation, with a focus on a novel tumor antigen delivery method using engineered exosomes, that we recently developed...
January 24, 2019: Cancers
María Celeste Nicolao, Christian Rodriguez Rodrigues, Andrea C Cumino
The secretion of extracellular vesicles (EVs) in helminth parasites is a constitutive mechanism that promotes survival by improving their colonization and adaptation in the host tissue. In the present study, we analyzed the production of EVs from supernatants of cultures of Echinococcus granulosus protoscoleces and metacestodes and their interaction with dendritic cells, which have the ability to efficiently uptake and process microbial antigens, activating T lymphocytes. To experimentally increase the release of EVs, we used loperamide, a calcium channel blocker that increases the cytosolic calcium level in protoscoleces and EV secretion...
January 2019: PLoS Neglected Tropical Diseases
Jieyu Li, Shenglan Huang, Zhifeng Zhou, Wansong Lin, Shuping Chen, Mingshui Chen, Yunbin Ye
Background: Dendritic cell (DC)-derived exosomes (Dexs) have been proved to induce and enhance antigen-specific T cell responses in vivo , and previous clinical trials have shown the feasibility and safety of Dexs in multiple human cancers. However, there is little knowledge on the efficacy of Dexs against hepatocellular carcinoma (HCC) until now. Methods: In this study, human peripheral blood-derived DCs were loaded with recombinant adeno-associated viral vector (rAAV)-carrying alpha-fetoprotein ( AFP ) gene (rAAV/AFP), and high-purity Dexs were generated...
2018: Cancer Management and Research
Brennetta J Crenshaw, Linlin Gu, Brian Sims, Qiana L Matthews
Introduction: Exosomes are extracellular vesicles that originate as intraluminal vesicles during the process of multivescular body formation. Exosomes mediate intercellular transfer of functional proteins, lipids, and RNAs. The investigation into the formation and role of exosomes in viral infections is still being elucidated. Exosomes and several viruses share similar structural and molecular characteristics. Explanation: It has been documented that viral hijacking exploits the exosomal pathway and mimics cellular protein trafficking...
2018: Open Virology Journal
Rong Li, Rajni Chibbar, Jim Xiang
Breast cancer is the leading cause of death in women globally. The human epidermal growth factor receptor 2 (HER2)-positive breast cancer is often associated with poor prognosis and high mortality. Even though anti-HER2 monoclonal antibodies have improved the clinical outcome, resistance to the antibody therapy becomes a major obstacle in the treatment of HER2-positive breast cancer patients. Alternative approaches are therefore needed. HER2-specific vaccines have been developed to trigger patient's immune system against HER2-positive breast cancer...
2018: OncoTargets and Therapy
Mohsen Keshavarz, Hamed Mirzaei, Maryam Salemi, Fatemeh Momeni, Mohammad Javad Mousavi, Mona Sadeghalvad, Yaser Arjeini, Farid Solaymani-Mohammadi, Javid Sadri Nahand, Haideh Namdari, Talat Mokhtari-Azad, Farhad Rezaei
The alarming rise of morbidity and mortality caused by influenza pandemics and epidemics has drawn attention worldwide since the last few decades. This life-threatening problem necessitates the development of a safe and effective vaccine to protect against incoming pandemics. The currently available flu vaccines rely on inactivated viral particles, M2e-based vaccine, live attenuated influenza vaccine (LAIV) and virus like particle (VLP). While inactivated vaccines can only induce systemic humoral responses, LAIV and VLP vaccines stimulate both humoral and cellular immune responses...
November 8, 2018: Reviews in Medical Virology
Adeleh Taghikhani, Zuhair Mohammad Hassan, Marzieh Ebrahimi, Seyyed-Mohammad Moazzeni
Tumor-derived exosomes (TEX) are known by their immune suppression effects as well as initiation mediators in cancer progression and metastasis. Meanwhile, they are appropriate sources to induce immunity against tumor cells, as consist of tumor specific and associated antigens. The aim of the current study is modifying TEX with microRNA miR-155, miR-142, and let-7i, to enhance their immune stimulation ability and induce potent dendritic cells (DC). For this, exosomes were isolated from mouse mammalian breast cancer cell line; 4T1, and subjected to miR-155, miR-142, and let-7i by electroporation...
October 26, 2018: Journal of Cellular Physiology
Shima Hadifar, Abolfazl Fateh, Mohammad Hadi Yousefi, Seyed Davar Siadat, Farzam Vaziri
Today, diagnosis, vaccination, and treatment of tuberculosis (TB) remain major clinical challenges. Therefore, an introduction of new diagnostic measures and biomarkers is necessary to improve infection control. The ideal biomarker for TB infection can be defined as a host or pathogen-derived biomolecule, which is potent for identifying infection and determining its clinical stage. Exosomes, defined as cell-derived nanovesicles released into biological fluids, are involved in cell-cell communication and immune modulation...
March 2019: Journal of Cellular Physiology
Sabari Nath Neerukonda, Nicholas A Egan, Joseph Patria, Imane Assakhi, Phaedra Tavlarides-Hontz, Shannon Modla, Eric R Muñoz, Matthew B Hudson, Mark S Parcells
Extracellular vesicles (EVs) is a collective term used to refer microparticles, exosomes, and apoptotic bodies produced by a variety of cells and released into interstitial spaces and bodily fluids. Serum exosomes can serve as invaluable biomarkers, containing m/miRNAs, lipids, and proteins, indicative of various conditions. There are currently limited studies on the characterization and mutual consensus of biomarker profiles of serum exosomes purified by different methods. Here we compared the advantages and disadvantages of two commonly used serum exosome purification procedures including ultracentrifugation (UC) and Total Exosome Isolation (TEI) reagent, by analyzing exosome size distribution, concentration, morphology and miRNA expression profiles...
October 11, 2018: Journal of Virological Methods
Sandra Jesus, Edna Soares, Maria Teresa Cruz, Olga Borges
Over the past few years, exosomes, a class of extracellular vesicles (EVs), have emerged as key players for inter-cellular communication ultimately modulating the behavior of target cells with countless outcomes. Nevertheless, the potential role of exosomes as vaccine adjuvants remains largely unexplored. Herein, we hypothesized that exosomes derived from immune cells may have an immunostimulatory effect and could constitute a good target towards the development of new fine-tuned vaccine adjuvants. To accomplish this goal, exosomes isolated from lipopolysaccharide endotoxin (LPS)-stimulated human monocytic cell line (THP-1) were characterized and tested for their non-specific immunostimulatory activity when administered subcutaneously to healthy mice; additionally, exosomes' vaccine adjuvant ability was also disclosed after their inclusion in vaccine formulations...
October 1, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Henry T Marshall, Mustafa B A Djamgoz
Host immunity recognizes and eliminates most early tumor cells, yet immunological checkpoints, exemplified by CTLA-4, PD-1, and PD-L1, pose a significant obstacle to effective antitumor immune responses. T-lymphocyte co-inhibitory pathways influence intensity, inflammation and duration of antitumor immunity. However, tumors and their immunosuppressive microenvironments exploit them to evade immune destruction. Recent PD-1 checkpoint inhibitors yielded unprecedented efficacies and durable responses across advanced-stage melanoma, showcasing potential to replace conventional radiotherapy regimens...
2018: Frontiers in Oncology
Flavia Ferrantelli, Francesco Manfredi, Chiara Chiozzini, Simona Anticoli, Eleonora Olivetta, Claudia Arenaccio, Maurizio Federico
Eukaryotic cells constitutively produce nanovesicles of 50-150 nm of diameter, referred to as exosomes, upon release of the contents of multivesicular bodies (MVBs). We recently characterized a novel, exosome-based way to induce cytotoxic T lymphocyte (CTL) immunization against full-length antigens. It is based on DNA vectors expressing products of fusion between the exosome-anchoring protein Nef mutant (Nefmut ) with the antigen of interest. The strong efficiency of Nefmut to accumulate in MVBs results in the production of exosomes incorporating huge amounts of the desired antigen...
November 2018: Molecular Biotechnology
Susan Bae, Jeffrey Brumbaugh, Benjamin Bonavida
The tumor microenvironment (TME) is a unique platform of cancer biology that considers the local cellular environment in which a tumor exists. Increasing evidence points to the TME as crucial for either promoting immune tumor rejection or protecting the tumor. The TME includes surrounding blood vessels, the extracellular matrix (ECM), a variety of immune and regulatory cells, and signaling factors. Exosomes have emerged to be molecular contributors in cancer biology, and to modulate and affect the constituents of the TME...
March 2018: Genes & Cancer
Zhenzhen Chen, Liangshun You, Lei Wang, Xianbo Huang, Hui Liu, Ju Ying Wei, Li Zhu, Wenbin Qian
BACKGROUND: Exosomes derived from tumor cells (TEXs) are involved in both immune suppression, angiogenesis, metastasis and anticancer stimulatory, but the biological characteristics and role of diffuse large B cell lymphoma (DLBCL)-derived exosomes have been less investigated. METHODS: Exosomes (EXOs) were isolated from OCI-LY3, SU-DHL-16, and Raji cells and biological characteristics of EXOs were investigated using electron microscopy, flow cytometry analysis, and Western blot analysis...
August 13, 2018: Journal of Experimental & Clinical Cancer Research: CR
Anton Deicher, Roland Andersson, Bobby Tingstedt, Gert Lindell, Monika Bauden, Daniel Ansari
Dendritic cells (DC) are an integral part of the tumor microenvironment. Pancreatic cancer is characterized by reduced number and function of DCs, which impacts antigen presentation and contributes to immune tolerance. Recent data suggest that exosomes can mediate communication between pancreatic cancer cells and DCs. Furthermore, levels of DCs may serve as prognostic factors. There is also growing evidence for the effectiveness of vaccination with DCs pulsed with tumor antigens to initiate adaptive cytolytic immune responses via T cells...
2018: Cancer Cell International
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