Skip to main content

Cancer Vaccines and Gut Microbiome: a rational approach to optimize cancer immunotherapy

Objective

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.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/mutation
  • /medical and health sciences/basic medicine/immunology/immunotherapy
  • /medical and health sciences/clinical medicine/oncology/cancer
  • /medical and health sciences/basic medicine/pharmacology and pharmacy/pharmaceutical drug/vaccines

Call for proposal

ERC-2018-ADG
See other projects for this call

Funding Scheme

ERC-ADG - Advanced Grant

Host institution

UNIVERSITA DEGLI STUDI DI TRENTO
Address
Via Calepina 14
38122 Trento
Italy
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 542 500

Beneficiaries (2)

UNIVERSITA DEGLI STUDI DI TRENTO
Italy
EU contribution
€ 1 542 500
Address
Via Calepina 14
38122 Trento
Activity type
Higher or Secondary Education Establishments
FONDAZIONE TOSCANA LIFE SCIENCES
Italy
EU contribution
€ 907 500
Address
Via Fiorentina 1
53100 Siena
Activity type
Research Organisations