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Peer-reviewedCC BYJournal of extracellular vesicles

Oncolytic Virus-Engineered Extracellular Vesicles Rewire Glioblastoma Immunity.

7 more authors
11 affiliations
  1. 1Tumor Microenvironment Laboratory, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
  2. 2Translational Medicine Doctoral School, Center of Postgraduate Medical Education, Warsaw, Poland.
  3. 3Laboratory of Sequencing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
  4. 4NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
  5. 5Department of Medical Microbiology, Medical University of Warsaw, Warsaw, Poland.
  6. 6The Laboratory of Cytometry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
  7. 7Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  8. 8Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland.
  9. 9Department of Biochemistry and Biotechnology, Poznań University of Life Sciences, Poznań, Poland.
  10. 10Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
  11. 11Department of NeuroOncology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.

Abstract

Immunotherapy with oncolytic Herpes simplex virus type 1 (oHSV-1) shows promise for glioblastoma; however, clinical benefit remains uncommon due to tumour- and host-mediated immunosuppression, which limits immune targeting of residual glioblastoma stem-like cells (GSCs). To address this barrier, extracellular vesicles (EVs) harvested from oHSV-1-infected GSCs (EVOV) were evaluated for their immunomodulatory capacity by priming peripheral blood mononuclear cells (PBMCs) ex vivo and in vivo. In GSC-PBMC organoids analysed by single-cell RNA sequencing, IFN-response and antigen-presentation programs were induced in both immune and tumour compartments, despite the GSC state. EVOV organoid transcriptome associated with patient tumour antigen-processing programs linked to improved clinical outcome, and EVOV immunopeptidomics identified candidate biomarker peptides that were also detected in patient immunopeptidomes from the clinical-trial cohort. In PBMC-engrafted NOD scid gamma mice bearing intracranial GSC xenografts, EVOV delivery increased circulating interferon (IFN) levels and enhanced systemic activation of T-cell subsets, while spatial transcriptomics revealed recruitment of peripheral immune cells to the tumour, accompanied by reprogramming of GSC states. Blocking vesicle-associated major histocompatibility complex I (MHC-I) attenuated EVOV-driven PBMC cytotoxicity against GSCs, supporting an MHC-I peptide-dependent mechanism of immune priming and a vaccine- or adjuvant-like, non-infectious, vesicle-based immunotherapeutic strategy.

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BibTeX
@article{kiel2026oncolytic,
  title = {{Oncolytic Virus-Engineered Extracellular Vesicles Rewire Glioblastoma Immunity.}},
  author = {Klaudia Kiel and Arpita Balakrishnan and Aleksandra Cabaj and Luiza Stanaszek and Maciej Przybylski and Dawid Stępnik and Marta Małuszek and Christopher Jannotta and Chiara Zoe Linke and Joanna Suszyńska-Zajczyk and Monika Knaur and Agnieszka Szczypiorowska and Szymon Hryhorowicz and Bianka Świderska and Katarzyna Piwocka and Alexander Lee Ling and E Antonio Chiocca and Agnieszka Bronisz and Jakub Godlewski},
  journal = {Journal of extracellular vesicles},
  year = {2026},
  month = oct,
  doi = {10.1002/jev2.70389},
  url = {https://europepmc.org/article/MED/42908192},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Oncolytic Virus-Engineered Extracellular Vesicles Rewire Glioblastoma Immunity.
AU  - Klaudia Kiel
AU  - Arpita Balakrishnan
AU  - Aleksandra Cabaj
AU  - Luiza Stanaszek
AU  - Maciej Przybylski
AU  - Dawid Stępnik
AU  - Marta Małuszek
AU  - Christopher Jannotta
AU  - Chiara Zoe Linke
AU  - Joanna Suszyńska-Zajczyk
AU  - Monika Knaur
AU  - Agnieszka Szczypiorowska
AU  - Szymon Hryhorowicz
AU  - Bianka Świderska
AU  - Katarzyna Piwocka
AU  - Alexander Lee Ling
AU  - E Antonio Chiocca
AU  - Agnieszka Bronisz
AU  - Jakub Godlewski
PY  - 2026
DA  - 2026/10/01
JO  - Journal of extracellular vesicles
DO  - 10.1002/jev2.70389
UR  - https://europepmc.org/article/MED/42908192
AB  - Immunotherapy with oncolytic Herpes simplex virus type 1 (oHSV-1) shows promise for glioblastoma; however, clinical benefit remains uncommon due to tumour- and host-mediated immunosuppression, which limits immune targeting of residual glioblastoma stem-like cells (GSCs). To address this barrier, extracellular vesicles (EVs) harvested from oHSV-1-infected GSCs (EVOV) were evaluated for their immunomodulatory capacity by priming peripheral blood mononuclear cells (PBMCs) ex vivo and in vivo. In GSC-PBMC organoids analysed by single-cell RNA sequencing, IFN-response and antigen-presentation programs were induced in both immune and tumour compartments, despite the GSC state. EVOV organoid transcriptome associated with patient tumour antigen-processing programs linked to improved clinical outcome, and EVOV immunopeptidomics identified candidate biomarker peptides that were also detected in patient immunopeptidomes from the clinical-trial cohort. In PBMC-engrafted NOD scid gamma mice bearing intracranial GSC xenografts, EVOV delivery increased circulating interferon (IFN) levels and enhanced systemic activation of T-cell subsets, while spatial transcriptomics revealed recruitment of peripheral immune cells to the tumour, accompanied by reprogramming of GSC states. Blocking vesicle-associated major histocompatibility complex I (MHC-I) attenuated EVOV-driven PBMC cytotoxicity against GSCs, supporting an MHC-I peptide-dependent mechanism of immune priming and a vaccine- or adjuvant-like, non-infectious, vesicle-based immunotherapeutic strategy.
SN  - 2001-3078
ER  -