Capture of antigen-bearing exosomes by DCs and cross-presentation of tumour antigen in exosomespreclinical study dataset
We have obtained data from a study where we addressed a model antigen to exosomes secreted by tumor cells in vivo, to allow capture of antigen-bearing exosomes by DCs and cross-presentation of the antigen. For this purpose, the model antigen OVA was fused to the C1C2 exosome-binding domain of MFG-E8/lactadherin. Tumors secreting the exosome-bound antigen grow slower than tumors secreting soluble OVA, because they induce activation of OVA-specific CD8+ T cells into killer cells. In addition, inducing in vivo secretion of the C1C2-coupled antigen by DNA vaccination induces prevention against subsequent tumor growth. These results show for the first time a function for exosome secretion in vivo. A paper describing these results has been published in 2008 (Zeelenberg et al., Cancer Research).
Our goal is now to develop the C1C2-based DNA vaccination approach to obtain an efficient anti-tumor therapeutic vaccine in mouse models. In parallel, we are analysing the mechanisms of exosome secretion in vitro. The goal of this project is to identify tools to inhibit or increase exosome secretion in vivo, and thus decipher their physiological roles, as well as modulate exosome-dependent immune responses.
- cell component type
- extracellular vesicular exosome
- experimental design type
- cellular modification design: antibody target experiment design