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Exosome vaccine

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
Julie M Diamond, Claire Vanpouille-Box, Sheila Spada, Nils-Petter Rudqvist, Jessica R Chapman, Beatrix M Ueberheide, Karsten A Pilones, Yasmeen Sarfraz, Silvia C Formenti, Sandra Demaria
Radiotherapy (RT) used at immunogenic doses leads to accumulation of cytosolic double-stranded DNA (dsDNA) in cancer cells, which activates type I IFN (IFN-I) via the cGAS/STING pathway. Cancer cell-derived IFN-I is required to recruit BATF3-dependent dendritic cells (DC) to poorly immunogenic tumors and trigger antitumor T-cell responses in combination with immune checkpoint blockade. We have previously demonstrated that the exonuclease TREX1 regulates radiation immunogenicity by degrading cytosolic dsDNA...
August 2018: Cancer Immunology Research
Zehuan Li, Yiran Qiu, Weiqi Lu, Ying Jiang, Jin Wang
Triple Negative Breast Cancer (TNBC) is a highly heterogeneous subtype of breast cancer that lacks the expression of oestrogen receptors, progesterone receptors and human epidermal growth factor receptor 2. Although TNBC is sensitive to chemotherapy, the overall outcomes of TNBC are worse than for other breast cancers, and TNBC is still one of the most fatal diseases for women. With the discovery of antigens specifically expressed in TNBC cells and the developing technology of monoclonal antibodies, chimeric antigen receptors and cancer vaccines, immunotherapy is emerging as a novel promising option for TNBC...
May 30, 2018: Journal of Translational Medicine
Marco Tucci, Francesco Mannavola, Anna Passarelli, Luigia Stefania Stucci, Mauro Cives, Franco Silvestris
Exosomes (Exo) are small vesicles produced by melanoma cells and the accessory cells of the tumor microenvironment. They emerge via both classical and direct pathways and actively participate in tumor colonisation of distant tissues. The proteins, nucleic acids, cytokines and growth factors engulfed by Exo are transferred to recipient cells, where they drive numerous functions required for the tumor escape from immune system control and tumor progression. By positively or negatively modulating immune cell properties, Exo provoke immune suppression and, in turn, defective dendritic cell (DC) functions...
April 17, 2018: Oncotarget
Francisco M Barros, Fatima Carneiro, Jose C Machado, Sónia A Melo
Exosomes are a type of extracellular vesicle whose study has grown exponentially in recent years. This led to the understanding that these structures, far from being inert waste by-products of cellular functioning, are active players in intercellular communication mechanisms, including in the interactions between cancer cells and the immune system. The deep comprehension of the crosstalk between tumors and the immune systems of their hosts has gained more and more importance, as immunotherapeutic techniques have emerged as viable options for several types of cancer...
2018: Frontiers in Immunology
Vignesh Sundararajan, Fazlul H Sarkar, Thamil Selvee Ramasamy
BACKGROUND: Recent advances in cancer biology have highlighted the relevance of exosomes and nanovesicles as carriers of genetic and biological messages between cancer cells and their immediate and/or distant environments. It has been found that these molecular cues may play significant roles in cancer progression and metastasis. Cancer cells secrete exosomes containing diverse molecules that can be transferred to recipient cells and/or vice versa to induce a plethora of biological processes, including angiogenesis, metastasis formation, therapeutic resistance, epithelial-mesenchymal transition and epigenetic/stemness (re)programming...
June 2018: Cellular Oncology (Dordrecht)
Romina Alfonsi, Ludovica Grassi, Michele Signore, Désirée Bonci
In recent years many articles have underlined the key role of nanovesicles, i.e., exosomes, as information carriers among biological systems including cancer. Tumor-derived exosomes (TEXs) are key players in the dynamic crosstalk between cancer cells and the microenvironment while promote immune system control evasion. In fact, tumors are undoubtedly capable of silencing the immune response through multiple mechanisms, including the release of exosomes. TEXs have been shown to boost tumor growth and promote progression and metastatic spreading via suppression or stimulation of the immune response towards cancer cells...
April 13, 2018: International Journal of Molecular Sciences
Stefan Schülke
Dendritic cells (DCs) are gatekeepers of the immune system that control induction and polarization of primary, antigen-specific immune responses. Depending on their maturation/activation status, the molecules expressed on their surface, and the cytokines produced DCs have been shown to either elicit immune responses through activation of effector T cells or induce tolerance through induction of either T cell anergy, regulatory T cells, or production of regulatory cytokines. Among the cytokines produced by tolerogenic DCs, interleukin 10 (IL-10) is a key regulatory cytokine limiting und ultimately terminating excessive T-cell responses to microbial pathogens to prevent chronic inflammation and tissue damage...
2018: Frontiers in Immunology
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