Cancer Vaccines and Gut Microbiome a rational approach to optimize cancer immu...
Cancer Vaccines and Gut Microbiome a rational approach to optimize cancer immunotherapy
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...
ver más
¿Tienes un proyecto y buscas un partner? Gracias a nuestro motor inteligente podemos recomendarte los mejores socios y ponerte en contacto con ellos. Te lo explicamos en este video
Proyectos interesantes
PowerMiT
Leveraging the impact of gut microbes to advance the efficac...
2M€
Cerrado
MiTE
Developing the next generation of cis-targeting macrophage-T...
150K€
Cerrado
CAN-IT-BARRIERS
Disruption of systemic and microenvironmental barriers to i...
3M€
Cerrado
CAR-TIME
Drivers and Brakes of CAR T Cell Efficacy Determined by the...
1M€
Cerrado
PeptiCHIP
PEPTICHIP Streamlined identification of tumour neoantigens...
150K€
Cerrado
Mel-Immune
An integrative genetic approach for the exploration of melan...
3M€
Cerrado
Información proyecto VACCIBIOME
Duración del proyecto: 62 meses
Fecha Inicio: 2019-06-04
Fecha Fin: 2024-08-31
Descripción del proyecto
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.