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Synthetic bacterial vesicles combined with tumour extracellular vesicles as cancer immunotherapy

Park, Kyong‐Su ; Svennerholm, Kristina ; Crescitelli, Rossella ; Lässer, Cecilia ; Gribonika, Inta ; Lötvall, Jan

Journal of extracellular vesicles, 2021-07, Vol.10 (9), p.e12120-n/a [Periódico revisado por pares]

United States: John Wiley and Sons Inc

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Título:
Synthetic bacterial vesicles combined with tumour extracellular vesicles as cancer immunotherapy
Autor: Park, Kyong‐Su ; Svennerholm, Kristina ; Crescitelli, Rossella ; Lässer, Cecilia ; Gribonika, Inta ; Lötvall, Jan
Assuntos: Adjuvants, Immunologic - metabolism ; Animals ; Artificial Cells - immunology ; Bacterial Outer Membrane - immunology ; Bacterial Outer Membrane - metabolism ; biogenesis ; Cancer and Oncology ; cancer immunotherapy ; Cancer och onkologi ; Cell Biology ; Cell Line, Tumor ; Cytokines - metabolism ; Dendritic Cells ; Escherichia coli - immunology ; escherichia-coli ; exosomes ; expression ; extracellular vesicles ; Extracellular Vesicles - immunology ; Extracellular Vesicles - metabolism ; Humans ; Immune Checkpoint Inhibitors - therapeutic use ; Immunization ; Immunotherapy ; inflammation ; innate ; Melanoma, Experimental - immunology ; Melanoma, Experimental - therapy ; Mice ; Mice, Inbred C57BL ; outer-membrane vesicles ; synthetic bacterial vesicles ; t-cells ; Th1 Cells - immunology ; tumour tissue ; tumour tissue extracellular vesicles ; vaccine
É parte de: Journal of extracellular vesicles, 2021-07, Vol.10 (9), p.e12120-n/a
Descrição: 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.
Editor: United States: John Wiley and Sons Inc
Idioma: Inglês

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Synthetic bacterial vesicles combined with tumour extracellular vesicles as cancer immunotherapy

Park, Kyong‐Su ; Svennerholm, Kristina ; Crescitelli, Rossella ; Lässer, Cecilia ; Gribonika, Inta ; Lötvall, Jan

United States: John Wiley and Sons Inc

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