Summary
ISV is a promising immunotherapy strategy which envisages the direct injection of immunomostimulatory reagents into the tumor mass. ISV offers the advantage to reduce off-target toxicity and to induce potent inflammation where cancer antigens have the maximal concentration. Different substances are being exploited in ISV and they include adjuvants, lytic viruses, cytokines/chemokines, antibodies. The rationale is to recruit antigen-presenting cells, T cells, NK cells and macrophages, thus promoting a strong anti-tumor immunity. Two ISV products are available and others are expected to come in the near future. Similarly to other cancer therapies, the current ISV strategies need to be optimized to improve their efficacy. In this proposal we wish to demonstrate the strength of a novel approach of ISV optimization based on two main innovative solutions. First, we plan to couple ISV to the oral administration of Bifidobacterium, a probiotic that, in the context of the Advanced ERC Grant “Vaccibiome”, we have shown to promote the remodeling of the gut microbiome and the tumor infiltration of T cells. Second, we propose to treat tumors with engineered bacterial Outer Membrane Vesicles (OMVs). OMVs are naturally decorated with a number of immunostimulatory molecules and we have already demonstrated the effectiveness of E. coli OMVs in different tumor mouse models. We plan to exploit our proprietary OMV engineering strategies to further potentiate OMV adjuvanticity by decorating them with Flt3L, a chemokine known to recruit immune cells. The combination of Bifidobacterium and Flt3L-OMVs will create a “perfect immunological storm” at the tumor site capable of eliminating both primary and metastatic tumors. Considering its simplicity and low production costs, our Microbiome-ISV therapy has the potential to become a broadly applicable neoadjuvant therapy to be performed before surgery in a large panel of solid tumors.
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| Web resources: | https://cordis.europa.eu/project/id/101111780 |
| Start date: | 01-06-2023 |
| End date: | 30-11-2024 |
| Total budget - Public funding: | - 150 000,00 Euro |
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Original description
ISV is a promising immunotherapy strategy which envisages the direct injection of immunomostimulatory reagents into the tumor mass. ISV offers the advantage to reduce off-target toxicity and to induce potent inflammation where cancer antigens have the maximal concentration. Different substances are being exploited in ISV and they include adjuvants, lytic viruses, cytokines/chemokines, antibodies. The rationale is to recruit antigen-presenting cells, T cells, NK cells and macrophages, thus promoting a strong anti-tumor immunity. Two ISV products are available and others are expected to come in the near future. Similarly to other cancer therapies, the current ISV strategies need to be optimized to improve their efficacy. In this proposal we wish to demonstrate the strength of a novel approach of ISV optimization based on two main innovative solutions. First, we plan to couple ISV to the oral administration of Bifidobacterium, a probiotic that, in the context of the Advanced ERC Grant “Vaccibiome”, we have shown to promote the remodeling of the gut microbiome and the tumor infiltration of T cells. Second, we propose to treat tumors with engineered bacterial Outer Membrane Vesicles (OMVs). OMVs are naturally decorated with a number of immunostimulatory molecules and we have already demonstrated the effectiveness of E. coli OMVs in different tumor mouse models. We plan to exploit our proprietary OMV engineering strategies to further potentiate OMV adjuvanticity by decorating them with Flt3L, a chemokine known to recruit immune cells. The combination of Bifidobacterium and Flt3L-OMVs will create a “perfect immunological storm” at the tumor site capable of eliminating both primary and metastatic tumors. Considering its simplicity and low production costs, our Microbiome-ISV therapy has the potential to become a broadly applicable neoadjuvant therapy to be performed before surgery in a large panel of solid tumors.Status
SIGNEDCall topic
ERC-2022-POC2Update Date
31-07-2023
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