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

Author:

Caproni Elena1ORCID,Corbellari Riccardo2ORCID,Tomasi Michele2ORCID,Isaac Samine J.2,Tamburini Silvia2ORCID,Zanella Ilaria2,Grigolato Martina2,Gagliardi Assunta1,Benedet Mattia1,Baraldi Chiara2,Croia Lorenzo2,Di Lascio Gabriele1,Berti Alvise2ORCID,Valensin Silvia1,Bellini Erika1,Parri Matteo3,Grandi Alberto14,Grandi Guido2ORCID

Affiliation:

1. Toscana Life Sciences Foundation, Via Fiorentina 1, 53100 Siena, Italy

2. Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Trento, Italy

3. Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Viale Morgagni 50, 50134 Florence, Italy

4. BiOMViS Srl, Via Fiorentina 1, 53100 Siena, Italy

Abstract

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 E. coli 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.

Funder

European Research Council

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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