Dendritic Cell Based Immunotheraphies
Dendritic cell (DC)-based immunotherapy is a booming field in which autologous DCs are trained ex vivo to prime T cells for targeting and destroying tumor cells. Whereas the safety of DC-based immunotherapy is clinically proven, empowering its efficacy remains a great challenge as the ex vivo trained DCs struggle to migrate to lymph nodes in order to present their antigens. Virtually, the majority of the injected DCs remain clustered at the site of injection, with only less then 5% of them being able to reach the lymph node. Therefore, the aim of this project is to improve the DC cell migration potential trough an innovative in vitro training on selected surface topographies (TopoChip) prior to injection. Specifically, DCs will be cultured on the TopoChip consisting of 2176 different surface topographies, in order to select the hits that can boost DCs movement to the lymph nodes in vivo. The engineered metabolically active DCs showing an enhanced migratory phenotype are described here as ‘aDCMoviE; Dendritic Cell (DC) Migration Engineering via Surface Topographies’. High content imaging of CCR7 and CD83 expression in combination with podosome formation will be performed to assess successful migration on TopoChips. After DCs are cultured on hit surfaces, an in vitro hydrogel-based 3D biomicrofluidic platform will be used for cytokine-induced chemotaxis to determine DC functionality.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 754462.