Anti-Tumor Efficacy of In Situ Vaccination Using Bacterial Outer Membrane Vesicles

In situ vaccination (ISV) is a promising cancer immunotherapy strategy that consists of the intratumoral administration of immunostimulatory molecules (adjuvants). The rationale is that tumor antigens are abundant at the tumor site, and therefore, to elicit an effective anti-tumor immune response, a...

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Main Authors: Elena Caproni, Riccardo Corbellari, Michele Tomasi, Samine J. Isaac, Silvia Tamburini, Ilaria Zanella, Martina Grigolato, Assunta Gagliardi, Mattia Benedet, Chiara Baraldi, Lorenzo Croia, Gabriele Di Lascio, Alvise Berti, Silvia Valensin, Erika Bellini, Matteo Parri, Alberto Grandi, Guido Grandi
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/15/13/3328
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author Elena Caproni
Riccardo Corbellari
Michele Tomasi
Samine J. Isaac
Silvia Tamburini
Ilaria Zanella
Martina Grigolato
Assunta Gagliardi
Mattia Benedet
Chiara Baraldi
Lorenzo Croia
Gabriele Di Lascio
Alvise Berti
Silvia Valensin
Erika Bellini
Matteo Parri
Alberto Grandi
Guido Grandi
author_facet Elena Caproni
Riccardo Corbellari
Michele Tomasi
Samine J. Isaac
Silvia Tamburini
Ilaria Zanella
Martina Grigolato
Assunta Gagliardi
Mattia Benedet
Chiara Baraldi
Lorenzo Croia
Gabriele Di Lascio
Alvise Berti
Silvia Valensin
Erika Bellini
Matteo Parri
Alberto Grandi
Guido Grandi
author_sort Elena Caproni
collection DOAJ
description In situ vaccination (ISV) is a promising cancer immunotherapy strategy that consists of the intratumoral administration of immunostimulatory molecules (adjuvants). The rationale is that tumor antigens are abundant at the tumor site, and therefore, to elicit an effective anti-tumor immune response, all that is needed is an adjuvant, which can turn the immunosuppressive environment into an immunologically active one. Bacterial outer membrane vesicles (OMVs) are potent adjuvants since they contain several microbe-associated molecular patterns (MAMPs) naturally present in the outer membrane and in the periplasmic space of Gram-negative bacteria. Therefore, they appear particularly indicted for ISV. In this work, we first show that the OMVs from <i>E. coli</i> BL21(DE3)Δ60 strain promote a strong anti-tumor activity when intratumorally injected into the tumors of three different mouse models. Tumor inhibition correlates with a rapid infiltration of DCs and NK cells. We also show that the addition of neo-epitopes to OMVs synergizes with the vesicle adjuvanticity, as judged by a two-tumor mouse model. Overall, our data support the use of the OMVs in ISV and indicate that ISV efficacy can benefit from the addition of properly selected tumor-specific neo-antigens.
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spelling doaj.art-2acb1d1e5f1248ffb5ad00bf1871451c2023-11-18T16:15:24ZengMDPI AGCancers2072-66942023-06-011513332810.3390/cancers15133328Anti-Tumor Efficacy of In Situ Vaccination Using Bacterial Outer Membrane VesiclesElena Caproni0Riccardo Corbellari1Michele Tomasi2Samine J. Isaac3Silvia Tamburini4Ilaria Zanella5Martina Grigolato6Assunta Gagliardi7Mattia Benedet8Chiara Baraldi9Lorenzo Croia10Gabriele Di Lascio11Alvise Berti12Silvia Valensin13Erika Bellini14Matteo Parri15Alberto Grandi16Guido Grandi17Toscana Life Sciences Foundation, Via Fiorentina 1, 53100 Siena, ItalyDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Trento, ItalyToscana Life Sciences Foundation, Via Fiorentina 1, 53100 Siena, ItalyToscana Life Sciences Foundation, Via Fiorentina 1, 53100 Siena, ItalyDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Trento, ItalyToscana Life Sciences Foundation, Via Fiorentina 1, 53100 Siena, ItalyDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Trento, ItalyToscana Life Sciences Foundation, Via Fiorentina 1, 53100 Siena, ItalyToscana Life Sciences Foundation, Via Fiorentina 1, 53100 Siena, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Viale Morgagni 50, 50134 Florence, ItalyToscana Life Sciences Foundation, Via Fiorentina 1, 53100 Siena, ItalyDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Trento, ItalyIn situ vaccination (ISV) is a promising cancer immunotherapy strategy that consists of the intratumoral administration of immunostimulatory molecules (adjuvants). The rationale is that tumor antigens are abundant at the tumor site, and therefore, to elicit an effective anti-tumor immune response, all that is needed is an adjuvant, which can turn the immunosuppressive environment into an immunologically active one. Bacterial outer membrane vesicles (OMVs) are potent adjuvants since they contain several microbe-associated molecular patterns (MAMPs) naturally present in the outer membrane and in the periplasmic space of Gram-negative bacteria. Therefore, they appear particularly indicted for ISV. In this work, we first show that the OMVs from <i>E. coli</i> BL21(DE3)Δ60 strain promote a strong anti-tumor activity when intratumorally injected into the tumors of three different mouse models. Tumor inhibition correlates with a rapid infiltration of DCs and NK cells. We also show that the addition of neo-epitopes to OMVs synergizes with the vesicle adjuvanticity, as judged by a two-tumor mouse model. Overall, our data support the use of the OMVs in ISV and indicate that ISV efficacy can benefit from the addition of properly selected tumor-specific neo-antigens.https://www.mdpi.com/2072-6694/15/13/3328cancer vaccinesneo-epitopespersonalized medicineouter membrane vesicles (OMVs)adjuvants
spellingShingle Elena Caproni
Riccardo Corbellari
Michele Tomasi
Samine J. Isaac
Silvia Tamburini
Ilaria Zanella
Martina Grigolato
Assunta Gagliardi
Mattia Benedet
Chiara Baraldi
Lorenzo Croia
Gabriele Di Lascio
Alvise Berti
Silvia Valensin
Erika Bellini
Matteo Parri
Alberto Grandi
Guido Grandi
Anti-Tumor Efficacy of In Situ Vaccination Using Bacterial Outer Membrane Vesicles
Cancers
cancer vaccines
neo-epitopes
personalized medicine
outer membrane vesicles (OMVs)
adjuvants
title Anti-Tumor Efficacy of In Situ Vaccination Using Bacterial Outer Membrane Vesicles
title_full Anti-Tumor Efficacy of In Situ Vaccination Using Bacterial Outer Membrane Vesicles
title_fullStr Anti-Tumor Efficacy of In Situ Vaccination Using Bacterial Outer Membrane Vesicles
title_full_unstemmed Anti-Tumor Efficacy of In Situ Vaccination Using Bacterial Outer Membrane Vesicles
title_short Anti-Tumor Efficacy of In Situ Vaccination Using Bacterial Outer Membrane Vesicles
title_sort anti tumor efficacy of in situ vaccination using bacterial outer membrane vesicles
topic cancer vaccines
neo-epitopes
personalized medicine
outer membrane vesicles (OMVs)
adjuvants
url https://www.mdpi.com/2072-6694/15/13/3328
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