Journal of Extracellular Vesicles最新文献

{"title":"Extracellular Vesicles From Human Fallopian Tubes Enhance IVF Embryo Development and Contain Functional Proteins Including YWHAZ","authors":"Yuehan Li,&nbsp;Wenjing Xiong,&nbsp;Limin Gao,&nbsp;Mingwei Lv,&nbsp;Fei Li,&nbsp;Rui Long,&nbsp;Chang Liu,&nbsp;Jianbo Wei,&nbsp;Meng Wang,&nbsp;Chenlu Zhang,&nbsp;Qiuyu Yu,&nbsp;Na Guo,&nbsp;Lei Jin,&nbsp;Cong Sui","doi":"10.1002/jev2.70337","DOIUrl":"https://doi.org/10.1002/jev2.70337","url":null,"abstract":"<p>Extracellular vesicles (EVs) in the mammalian oviduct constitute a key maternal regulatory system that maintains redox balance during early embryogenesis, yet their molecular cargo and functional relevance in human embryos remain poorly defined. Here, we show that human Fallopian tube-derived EVs (oEVs) are rapidly internalized by human preimplantation embryos and improve developmental quality in vitro, increasing high-quality Day 3 embryo formation and blastocyst development. Label-free proteomics identified 6505 oEV proteins, with metabolic, antioxidant and stress-response pathways strongly enriched. Cross-reference with four independent datasets revealed a conserved protein subset shared across secretory-phase oviduct fluid, pluripotent stem cell-derived EVs and in-vivo-developed embryos; among these, YWHAZ was prioritized for functional validation because of its abundance in oEVs, its presence across embryo-related datasets, and its known involvement in stress-response pathways. We found that <i>Ywhaz</i>-deficient mouse embryos exhibit elevated oxidative and apoptotic stress, transcriptional signatures of impaired glutathione metabolism, and failure to survive to birth despite normal blastocyst morphology. Recombinant YWHAZ protein alone failed to enter intact embryos, whereas engineered YWHAZ-loaded EVs were efficiently internalized and significantly reduced intracellular ROS and apoptosis, restoring redox status towards in vivo levels without compromising implantation or foetal growth. Taken together, these findings identify YWHAZ protein as a conserved vesicle-delivered regulator of redox homeostasis and demonstrate that EV-mediated molecular delivery can partially rescue the oxidative stress burden characteristic of in vitro embryo culture. This work provides mechanistic insight into the maternal redox support system of the oviduct and establishes a foundation for EV-based engineering of next-generation embryo culture strategies.</p><p>Fallopian tube extracellular vesicles enhance human IVF embryo development by delivering functional proteins such as YWHAZ to regulate oxidative stress and blastocyst formation.</p><p>Large Scale Data\u0000\u0000 </p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 7","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70337","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EV-Checklist: AI-Powered Rapid Documentation for Enhancing Transparency and Accessibility of Extracellular Vesicle Research Data","authors":"Rodolphe Poupardin,&nbsp;Martin Wolf,&nbsp;Antri Stefani,&nbsp;Gregor Fuhrmann,&nbsp;Dirk Strunk","doi":"10.1002/jev2.70343","DOIUrl":"10.1002/jev2.70343","url":null,"abstract":"<p>Transition of extracellular vesicle (EV) research from basic discovery to clinical application raised hopes regarding diagnostic, therapeutic and prognostic progress. Rigorous reporting of experimental details is required to align the EV field with pharmaceutical quality standards. MISEV2023 recommendations encourage concise reporting but widespread adoption remains limited. Current reporting tools are time-consuming, and adherence declines despite rapidly growing number of EV studies. We therefore created EV-Checklist, a complementary digital tool that streamlines reporting and increases transparency. By uploading manuscript text, an AI-assisted algorithm automatically completes a checklist covering EV nomenclature, source, isolation, characterization and function. To ensure accuracy, users validate AI-generated entries before submission—ideally, gaps in reporting can be closed (e.g., missing particle/protein ratio). The resulting concise report can accompany manuscripts helping editors, reviewers and readers by presenting key methodological and results details at a glance. EV-Checklist complements existing comprehensive registries as ‘fast-and-easy’ tool enhancing clarity and accessibility of EV research data and may promote higher adherence to documentation standards. Adoption may be encouraged by journal endorsement to streamline the review process for compliant submissions, signalling adherence to MISEV2023 standards. EV-Checklist and an accompanying AI-assisted search tool (PMC EV Search), spanning over 45,700 open-access EV manuscripts, are publicly available at https://ev-zone.org/.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 7","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70343","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicle Release Within Energetic and Quantitative Constraints: Implications for Function","authors":"Christian Preußer,&nbsp;Elke Pogge von Strandmann","doi":"10.1002/jev2.70340","DOIUrl":"10.1002/jev2.70340","url":null,"abstract":"<p>Extracellular vesicles (EVs) are widely framed as dedicated mediators of intercellular communication. Several studies attribute signalling and regulatory functions to vesicle-associated cargo. However, functional interpretation is frequently inferred from detection and correlation, whereas quantitative and energetic boundary conditions remain underexamined. Here, an alternative but non-exclusive perspective is proposed: EV release is considered as a regulated consequence of membrane turnover and proteostatic balance in cells operating far from thermodynamic equilibrium. Vesicle formation represents an energetically permissible transition within a constrained membrane system. Communication may arise from this process, but it should not be presumed as its primary rationale. Any EV-mediated effect requires sequential steps such as encounter, uptake, cytosolic access, and sufficient cargo copy number, with each imposing limiting thresholds. At low mean copy numbers, stochastic partitioning and systemic dilution constrain reproducible impact. Enrichment alone does not establish functional sufficiency. This system does not deny EV function. It situates functional claims within explicit quantitative, statistical, and energetic boundary conditions and formulates experimentally testable criteria for their validation.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 7","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70340","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Profiling of Extracellular Vesicles Isolated from Boar Reproductive Fluids","authors":"Veronika Kraus,&nbsp;Barbora Doleckova,&nbsp;Michaela Frolikova,&nbsp;Ondrej Sanovec,&nbsp;Daniela Spevakova,&nbsp;Zuzana Pilsova,&nbsp;Aneta Pilsova,&nbsp;Katerina Komrskova,&nbsp;Ondrej Simonik,&nbsp;Pavla Postlerova","doi":"10.1002/jev2.70329","DOIUrl":"10.1002/jev2.70329","url":null,"abstract":"<p>Extracellular vesicles (EVs) are small membrane-bound structures that facilitate intercellular communication in the reproductive system, modulating gamete maturation, capacitation, immunomodulation and fertilization. Despite pigs’ high relevance as a biomedical model, many aspects of EV biology remain poorly understood. EVs from boar seminal plasma (SP-EVs) are relatively well studied, whereas epididymosomes remain largely uncharacterized. Therefore, this study aimed to isolate and characterize EVs from the caput, corpus and cauda regions of boar epididymis, as well as from SP, with their further precise analysis towards their interaction with sperm. We successfully obtained EVs from all studied fluids with sufficient purity. Importantly, our isolation protocol preserved the EVs’ ability to interact with sperm, demonstrated by lipophilic dye staining and biotin labelling experiments, confirming precisely their interaction and cargo transfer to sperm cells. Well-established EV markers, such as Alix and tetraspanins, were detected in the EVs, and additionally, phosphorylated, ubiquitinated and sialylated proteins were uniquely identified. Furthermore, we employed a proteomic approach to characterize EV proteins (mass spectrometry data are available via ProteomeXchange with identifier PXD074929) and investigate their functional roles using the Gene Ontology (GO) database. This study contributes valuable insights into the molecular composition and functional properties of EVs from the male reproductive tract. It may provide a solid framework for further basic and translational research in reproductive biology and biomedicine.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 7","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eliminating PD-L1 on Dendritic Cell Extracellular Vesicles for Immunotherapy Potentiates Immune-Mediated Tumour Rejection in Mice","authors":"Loes Teeuwen,&nbsp;Loïc Steiner,&nbsp;Chantal Reinhardt,&nbsp;Annemarijn Offens,&nbsp;Jesse E. Kuipers,&nbsp;Daniel Martínez-Martínez,&nbsp;Jules Mazouin,&nbsp;Benedict J. Chambers,&nbsp;Gözde Güçlüler Akpinar,&nbsp;Susanne Gabrielsson","doi":"10.1002/jev2.70322","DOIUrl":"https://doi.org/10.1002/jev2.70322","url":null,"abstract":"<p>Extracellular vesicles (EVs) are emerging as promising vehicles for cancer immunotherapy, yet the molecular determinants of their immunogenicity remain poorly defined. While PD-L1 expression on cancer-derived EVs has been shown to suppress immune responses, its role on immunotherapeutic EVs remains unexplored. In this study, we investigated how eliminating PD-L1 from antigen-loaded bone marrow-derived dendritic cell (BMDC) EVs affects the efficacy of EV-based cancer vaccines.</p><p>We generated and characterized ovalbumin (OVA)-loaded BMDC EVs from wild-type (WT) and PD-L1^−/− C57BL/6 mice. EVs were administered intravenously into WT mice in immunization experiments and in therapeutic and prophylactic B16 OVA-secreting melanoma models. Immune responses were assessed by flow cytometry, ELISpot, and ELISA, and tumour growth was monitored.</p><p>Proteomic analysis confirmed high EV purity and similar protein profiles between WT and PD-L1^−/− EVs, with PD-L1 being the major difference. Functionally, PD-L1^−/− EVs induced significantly stronger anti-tumour responses in vivo, particularly in the prophylactic setting. Mice treated with PD-L1^−/− EVs showed increased CD8⁺ T cell tumour infiltration, enhanced IFNγ secretion, and higher tumour rejection rates compared to WT EVs (72.7% vs. 37.5%). Additionally, the frequency of tumour-infiltrating, antigen-specific CD8⁺ T cells was significantly higher in PD-L1^−/− EV-treated mice.</p><p>In summary, BMDC-derived EVs loaded with antigen are potent immune stimulators, and removal of immune checkpoint molecules such as PD-L1 further enhances their immunogenicity. These findings support the development of engineered EVs as improved platforms for cancer immunotherapy.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 7","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70322","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing the Signal: The Metastasis Suppressor NDRG1 Disrupts Small Extracellular Vesicle-Mediated Crosstalk in Pancreatic Cancer","authors":"Jiawei Chang,&nbsp;Shafi Alenizi,&nbsp;Heloisa Zaccaron Milioli,&nbsp;Winston Lay,&nbsp;Saranya Pounraj,&nbsp;Yujie Li,&nbsp;Mekonnen Sisay Shiferaw,&nbsp;Elham Hosseini-Beheshti,&nbsp;Zaklina Kovacevic","doi":"10.1002/jev2.70334","DOIUrl":"https://doi.org/10.1002/jev2.70334","url":null,"abstract":"<p>Pancreatic cancer (PaC) remains one of the deadliest cancers, with 5-year survival rates of 13%. A major driver of its aggressiveness is the tumour microenvironment (TME), which fuels tumour growth, metastasis, and therapeutic resistance through dynamic, bi-directional communication between cancer cells, fibroblasts, and immune cells. Emerging evidence highlights extracellular vesicles (EVs) as key mediators of oncogenic cross-talk within the PaC TME. This study demonstrates for the first time that the overexpression of metastasis suppressor N-myc downstream regulated gene 1 (NDRG1) significantly influences the biogenesis, cargo packaging and release of EVs by cancer cells. This was mediated by a direct interaction between NDRG1 and ALIX, a key protein involved in EV biogenesis and packaging, with NDRG1 facilitating ALIX proteasomal degradation. Further, EVs released from NDRG1-overexpressing cells had significantly fewer CAF-activation proteins (i.e. TGF-β), leading to attenuated ERK1/2 and p38 activation in pancreatic stellate cells (PSCs), and reduced expression of key fibrotic markers (α-SMA, FAP, and collagen 1A). NDRG1 overexpression also reduced sEVs uptake by PaC cells and diverted these to the lysosome for degradation. These findings uncover a previously unrecognized mechanism by which NDRG1 overexpression disrupts the oncogenic two-way communication between PaC cells and the TME, positioning NDRG1 overexpression as a compelling therapeutic approach against this formidable malignancy.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 7","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70334","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Nuclear Magnetic Resonance into Bioprocess Control of Clinical-Grade Extracellular Vesicle Manufacturing","authors":"Santiago Roura,&nbsp;Núria Amigó,&nbsp;Joaquim Vives","doi":"10.1002/jev2.70330","DOIUrl":"https://doi.org/10.1002/jev2.70330","url":null,"abstract":"<p>The rapid advance in the research and development of extracellular vesicle (EV)-based therapeutics has stimulated a paradigm shift in the field of regenerative medicine. However, translating EV-based therapies into the clinic requires robust, scalable, and Good Manufacturing Practice (GMP)-compliant bioprocesses that ensure product consistency, potency and safety. In this <i>Perspective</i>, we propose that metabolomics, particularly by using high-resolution nuclear magnetic resonance (NMR), can serve as a transformative analytical technology in EV manufacturing and quality control. By integrating NMR-metabolomics monitoring into upstream cell culture and downstream EV purification workflows, it becomes possible to identify metabolic fingerprints predictive of cell performance, EV yield and EV bioactivity. Drawing from the experience of the GALVANO consortium, which is developing Spain's first GMP-grade platform for EV manufacturing from clinical-grade human Wharton Jelly's mesenchymal stromal cells (WJ-MSC-EVs) with particular promise in the modulation of inflammation and tissue regeneration, we highlight how NMR-metabolomics can support Quality by Design (QbD) principles, enhance in-process analytics and accelerate regulatory harmonisation. We further discuss the need for collaborative standardisation of analytical methods and reporting frameworks to ensure reproducibility and comparability across EV batches. Together, these strategies can advance EV-based therapeutics toward reliable, large-scale clinical application.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 7","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70330","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory Challenges and Opportunities for Cell-Derived Extracellular Vesicles in Pharmaceutical Development: A European and Global Perspective","authors":"Tania Limongi,&nbsp;Paola Milla,&nbsp;Barbara Stella,&nbsp;Silvia Arpicco","doi":"10.1002/jev2.70332","DOIUrl":"https://doi.org/10.1002/jev2.70332","url":null,"abstract":"<p>Cell-derived extracellular vesicles (EVs) attract growing interest as biologically active, acellular platforms for therapeutic and diagnostic use in regenerative medicine, immunomodulation, and drug delivery. While EV-based products advance into clinical development worldwide, their acellular nature maps non-uniformly onto pre-existing categories. In the European Union, the 2025 European Medicines Agency/Committee for Advanced Therapies (EMA/CAT) guideline clarifies that “not substantially modified extracellular vesicles” fall outside the current advanced therapy medicinal products (ATMPs) definition, requiring case-by-case development within other medicinal-product frameworks. Conversely, the United States Food and Drug Administration (FDA) regulates exosome/EV products for disease treatment as drugs and biological products subject to premarket requirements, while other regions apply existing drug and regenerative-medicine–related instruments using jurisdiction-specific classification criteria. This heterogeneity creates challenges for regulatory positioning, quality assessment, comparability, and cross-regional clinical development. We critically examine the evolving landscape of EV-based therapeutics, focusing on regulatory, technical, safety, and ethical considerations from a global perspective. We argue EV-based products should be developed within existing medicinal product frameworks (e.g., biologics, ATMP-related instruments), provided regulatory tools are applied consistently, and operational grey zones (e.g., classification criteria, critical quality attributes (CQAs), potency strategies, and comparability) are identified for clarification. Without proposing normative frameworks, this work provides a state-of-the-art synthesis intended to support ongoing regulatory dialogue across regions. The discussion is relevant for international agencies such as the EMA, FDA, the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan, the World Health Organization (WHO), and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), as well as for scientific societies such as the International Society for Extracellular Vesicles (ISEV) promoting methodological convergence. By aligning scientific insight with regulatory awareness, this review supports advancing EV-based therapies toward safe, reproducible, and internationally credible clinical use.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 7","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70332","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ISEV2026 Abstract Book","authors":"","doi":"10.1002/jev2.70321","DOIUrl":"https://doi.org/10.1002/jev2.70321","url":null,"abstract":"","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 S1","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70321","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148322421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Poxviruses Induce the Secretion of Immunostimulating and Anti-Tumoral Extracellular Vesicles","authors":"Lucas Walther,&nbsp;Vincent Mittelheisser,&nbsp;Marie-Christine Claudepierre,&nbsp;Louis Bochler,&nbsp;Magali Rompais,&nbsp;Jules Deforges,&nbsp;Nathalie Silvestre,&nbsp;Annabel Larnicol,&nbsp;Christine Carapito,&nbsp;Eric Quémeneur,&nbsp;Jacky G Goetz,&nbsp;Karola Rittner,&nbsp;Vincent Hyenne","doi":"10.1002/jev2.70307","DOIUrl":"10.1002/jev2.70307","url":null,"abstract":"<p>Poxvirus-based vectors provide a versatile cancer immunotherapy platform, enabling the expression of immunostimulatory molecules and cancer-specific antigens. While infections with pathogenic viruses are well known to modulate extracellular vesicle (EV) biogenesis and function, the extent to which therapeutic poxviral vectors influence EV secretion by immune cells and thereby affect therapeutic efficacy remains underexplored. In this study, we showed that poxviruses, including the clinically relevant Modified Vaccinia Ankara (MVA), stimulate the secretion of small EVs (sEVs) containing viral proteins and immune-related signatures from peripheral blood mononuclear cells (PBMCs). Using an engineered MVA vector, we demonstrated the transfer of virus-encoded therapeutic payloads to sEVs, including the model ovalbumin (OVA)-derived peptide SIINFEKL presented by the class I major histocompatibility complex (MHC I) and the immune activators interleukin-12 (IL-12) and CD40 ligand (CD40L). Depending on the isolation method, these sEVs stimulated SIINFEKL-specific CD8⁺ T cells with varying efficiencies in vitro. Remarkably, intravenous injection of these sEVs, but also of the soluble secretome from the same cells, into E.G7-OVA lymphoma–bearing mice reduced tumor growth to an extent comparable to the virus itself. Taken together, our findings indicate that EVs released from immune cells infected with engineered therapeutic poxviruses exert potent antitumor activity. These vesicles represent actionable mediators whose secretion and functionalization can be harnessed to improve viral vector–based immunotherapies, as well as being considered as therapeutic vectors in their own.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 6","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}