Summary
This proposal intends to shed light on the interplay between cancer immunity and gut microbiome as a way to optimize personalized cancer vaccines and immunotherapy. The project originates from two milestone discoveries. First, to be effective cancer immunotherapies have to target CD4+/CD8+ T cell neo-epitopes, which originate from tumor mutations. Second, the gut microbiome influences the effectiveness of anti-PD-1/PD-L1 antibody immunotherapy both in animal models and in humans. We also recently showed in a mouse model that oral gavages with Bifidobacterial cocktails improved the therapeutic power of neo-epitope-based cancer vaccines. How microbiome affects anti-cancer immunity has not been fully elucidated yet and a deep understanding of the underlying mechanisms has the potential to substantially improve cancer immunotherapy. Since microbiome antigens are processed and presented by antigen-presenting cells and microbiome-induced T cells represent large fraction of the peripheral T cell repertoire, our hypothesis is that this large repertoire includes T cells which cross-react with cancer neo-epitopes (“molecular mimicry (MM)”). Depending upon the composition of gut microbiome, cross-reacting T cells can positively or negatively modulate anti-tumor immunity. To demonstrate the role of MM in cancer immunity this project intends (i) to select the cross-reactive T cell epitopes as predicted by meta-omics analysis of gut microbiome and exome/transcriptome analysis of cancer cell lines, (ii) to formulate vaccines containing different combination of cross-reactive epitopes, and (iii) to test vaccine anti-tumor activities in normal mice, gnotobiotic mice and mice with engineered microbiome. The ultimate goals are: 1) to provide new criteria for neo-epitope selection in personalized cancer vaccines, 2) to develop prognostic tools based on microbiome analysis, and 3) to define microbial species to be used as immune-potentiators in patients undergoing cancer therapy.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/834634 |
| Start date: | 01-09-2019 |
| End date: | 31-08-2024 |
| Total budget - Public funding: | 2 450 000,00 Euro - 2 450 000,00 Euro |
Cordis data
Original description
This proposal intends to shed light on the interplay between cancer immunity and gut microbiome as a way to optimize personalized cancer vaccines and immunotherapy. The project originates from two milestone discoveries. First, to be effective cancer immunotherapies have to target CD4+/CD8+ T cell neo-epitopes, which originate from tumor mutations. Second, the gut microbiome influences the effectiveness of anti-PD-1/PD-L1 antibody immunotherapy both in animal models and in humans. We also recently showed in a mouse model that oral gavages with Bifidobacterial cocktails improved the therapeutic power of neo-epitope-based cancer vaccines. How microbiome affects anti-cancer immunity has not been fully elucidated yet and a deep understanding of the underlying mechanisms has the potential to substantially improve cancer immunotherapy. Since microbiome antigens are processed and presented by antigen-presenting cells and microbiome-induced T cells represent large fraction of the peripheral T cell repertoire, our hypothesis is that this large repertoire includes T cells which cross-react with cancer neo-epitopes (“molecular mimicry (MM)”). Depending upon the composition of gut microbiome, cross-reacting T cells can positively or negatively modulate anti-tumor immunity. To demonstrate the role of MM in cancer immunity this project intends (i) to select the cross-reactive T cell epitopes as predicted by meta-omics analysis of gut microbiome and exome/transcriptome analysis of cancer cell lines, (ii) to formulate vaccines containing different combination of cross-reactive epitopes, and (iii) to test vaccine anti-tumor activities in normal mice, gnotobiotic mice and mice with engineered microbiome. The ultimate goals are: 1) to provide new criteria for neo-epitope selection in personalized cancer vaccines, 2) to develop prognostic tools based on microbiome analysis, and 3) to define microbial species to be used as immune-potentiators in patients undergoing cancer therapy.Status
SIGNEDCall topic
ERC-2018-ADGUpdate Date
27-04-2024
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