Synthetic bacterial vesicles combined with tumour extracellular vesicles as cancer immunotherapy

Park, Kyong-SuGothenburg University,Göteborgs universitet,Institutionen för medicin,Krefting Research Centre,Institute of Medicine (författare)

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.

Svennerholm, Kristina,1981Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för anestesiologi och intensivvård,Institute of Clinical Sciences, Department of Anesthesiology and Intensive care(Swepub:gu)xskrix (författare)
Crescitelli, Rossella,1985Gothenburg University,Göteborgs universitet,Institutionen för medicin,Krefting Research Centre,Institute of Medicine(Swepub:gu)xcrero (författare)
Lässer, Cecilia,1981Gothenburg University,Göteborgs universitet,Institutionen för medicin,Krefting Research Centre,Institute of Medicine(Swepub:gu)xlasce (författare)
Gribonika, IntaGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology(Swepub:gu)xgribi (författare)
Lötvall, Jan,1956Gothenburg University,Göteborgs universitet,Krefting Research Centre,Institutionen för medicin,Institute of Medicine(Swepub:gu)xlotja (författare)
Göteborgs universitetInstitutionen för medicin (creator_code:org_t)

Av författaren/redakt...: Park, Kyong-Su; Svennerholm, Kri ...; Crescitelli, Ros ...; Lässer, Cecilia, ...; Gribonika, Inta; Lötvall, Jan, 19 ...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

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