Synthetic bacterial vesicles combined with tumour extracellular vesicles as cancer immunotherapy
Park, Kyong-Su ; Svennerholm, Kristina ; Crescitelli, Rossella ; Lässer, Cecilia ; Gribonika, Inta LU
and Lötvall, Jan
(2021)
In Journal of Extracellular Vesicles
10(9).
- Abstract
Bacterial outer membrane vesicles (OMV) have gained attention as a promising new cancer vaccine platform for efficiently provoking immune responses. However, OMV induce severe toxicity by activating the innate immune system. In this study, we applied a simple isolation approach to produce artificial OMV that we have named Synthetic Bacterial Vesicles (SyBV) that do not induce a severe toxic response. We also explored the potential of SyBV as an immunotherapy combined with tumour extracellular vesicles to induce anti-tumour immunity. Bacterial SyBV were produced with high yield by a protocol including lysozyme and high pH treatment, resulting in pure vesicles with very few cytosolic components and no RNA or DNA. These SyBV did not cause... (More)
Bacterial outer membrane vesicles (OMV) have gained attention as a promising new cancer vaccine platform for efficiently provoking immune responses. However, OMV induce severe toxicity by activating the innate immune system. In this study, we applied a simple isolation approach to produce artificial OMV that we have named Synthetic Bacterial Vesicles (SyBV) that do not induce a severe toxic response. We also explored the potential of SyBV as an immunotherapy combined with tumour extracellular vesicles to induce anti-tumour immunity. Bacterial SyBV were produced with high yield by a protocol including lysozyme and high pH treatment, resulting in pure vesicles with very few cytosolic components and no RNA or DNA. These SyBV did not cause systemic pro-inflammatory cytokine responses in mice compared to naturally released OMV. However, SyBV and OMV were similarly effective in activation of mouse bone marrow-derived dendritic cells. Co-immunization with SyBV and melanoma extracellular vesicles elicited tumour regression in melanoma-bearing mice through Th-1 type T cell immunity and balanced antibody production. Also, the immunotherapeutic effect of SyBV was synergistically enhanced by anti-PD-1 inhibitor. Moreover, SyBV displayed significantly greater adjuvant activity than other classical adjuvants. Taken together, these results demonstrate a safe and efficient strategy for eliciting specific anti-tumour responses using immunotherapeutic bacterial SyBV.
(Less)
- author
- Park, Kyong-Su
; Svennerholm, Kristina
; Crescitelli, Rossella
; Lässer, Cecilia
; Gribonika, Inta
LU
and Lötvall, Jan
- publishing date
- 2021-07
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adjuvants, Immunologic/metabolism, Animals, Artificial Cells/immunology, Bacterial Outer Membrane/immunology, Cell Line, Tumor, Cytokines/metabolism, Dendritic Cells, Escherichia coli/immunology, Extracellular Vesicles/immunology, Humans, Immune Checkpoint Inhibitors/therapeutic use, Immunization, Immunotherapy, Melanoma, Experimental/immunology, Mice, Mice, Inbred C57BL, Th1 Cells/immunology
- in
- Journal of Extracellular Vesicles
- volume
- 10
- issue
- 9
- article number
- e12120
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:85111160553
- pmid:34262675
- ISSN
- 2001-3078
- DOI
- 10.1002/jev2.12120
- language
- English
- LU publication?
- no
- additional info
- © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.
- id
- d588d8e1-b1e8-4900-91f7-4400ea385d89
- date added to LUP
- 2025-12-20 13:29:09
- date last changed
- 2025-12-22 14:34:42
@article{d588d8e1-b1e8-4900-91f7-4400ea385d89,
abstract = {{<p>Bacterial outer membrane vesicles (OMV) have gained attention as a promising new cancer vaccine platform for efficiently provoking immune responses. However, OMV induce severe toxicity by activating the innate immune system. In this study, we applied a simple isolation approach to produce artificial OMV that we have named Synthetic Bacterial Vesicles (SyBV) that do not induce a severe toxic response. We also explored the potential of SyBV as an immunotherapy combined with tumour extracellular vesicles to induce anti-tumour immunity. Bacterial SyBV were produced with high yield by a protocol including lysozyme and high pH treatment, resulting in pure vesicles with very few cytosolic components and no RNA or DNA. These SyBV did not cause systemic pro-inflammatory cytokine responses in mice compared to naturally released OMV. However, SyBV and OMV were similarly effective in activation of mouse bone marrow-derived dendritic cells. Co-immunization with SyBV and melanoma extracellular vesicles elicited tumour regression in melanoma-bearing mice through Th-1 type T cell immunity and balanced antibody production. Also, the immunotherapeutic effect of SyBV was synergistically enhanced by anti-PD-1 inhibitor. Moreover, SyBV displayed significantly greater adjuvant activity than other classical adjuvants. Taken together, these results demonstrate a safe and efficient strategy for eliciting specific anti-tumour responses using immunotherapeutic bacterial SyBV.</p>}},
author = {{Park, Kyong-Su and Svennerholm, Kristina and Crescitelli, Rossella and Lässer, Cecilia and Gribonika, Inta and Lötvall, Jan}},
issn = {{2001-3078}},
keywords = {{Adjuvants, Immunologic/metabolism; Animals; Artificial Cells/immunology; Bacterial Outer Membrane/immunology; Cell Line, Tumor; Cytokines/metabolism; Dendritic Cells; Escherichia coli/immunology; Extracellular Vesicles/immunology; Humans; Immune Checkpoint Inhibitors/therapeutic use; Immunization; Immunotherapy; Melanoma, Experimental/immunology; Mice; Mice, Inbred C57BL; Th1 Cells/immunology}},
language = {{eng}},
number = {{9}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Journal of Extracellular Vesicles}},
title = {{Synthetic bacterial vesicles combined with tumour extracellular vesicles as cancer immunotherapy}},
url = {{http://dx.doi.org/10.1002/jev2.12120}},
doi = {{10.1002/jev2.12120}},
volume = {{10}},
year = {{2021}},
}