560kE KWF Grant for department of TIL

Brok den, Martijn

Gosse Adema en Martijn den Brok department of Tumor Immunology have received a 560 kE KWF Grant. 

Saponin-based adjuvants in anti-tumor immunity: a role for lipid bodies in adjuvanticity?


Adjuvants comprise a diverse group of compounds, which are used to enhance the effectiveness of (cancer) vaccines. For human vaccines, registered adjuvants are limited and include aluminum- and oil/water-based adjuvants. These adjuvants induce robust antibody responses, but appear weak in building cell-mediated immunity. In animal vaccines additional adjuvants are in use, including saponin-based adjuvants (SBAs) that do enforce T cell-mediated immunity. Despite the growing need to understand how vaccines work, the exact immunological mechanisms of the classical immune adjuvants remain poorly defined.

We found in our model for in situ tumor ablation that co-injection of saponin-based adjuvants (SBAs) induced superior protective anti-tumor immunity relative to other non-microbial and microbial adjuvants. This unique anti-tumor effect was accompanied by enhanced antigen cross-presentation by dendritic cells (DC), and high numbers of tumor-specific CTLs. The outcome could even be further enhanced when a combination was made with a TLR9 ligand. In search for a mechanism, we uncovered a remarkable relation between SBAs and DC functionality. Our data now link SBA-exposure of DCs to highly effective  antigen cross-presentation and cytokine production. To further resolve how SBAs improve immune responses we propose to study DC function following adjuvant exposure in mice and man in relation to cancer vaccines. 


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