During the project, the main experimental platforms required for the development of the proposed nanoimmunotherapy were established and optimised. A non-soluble mesothelin-targeted CAR construct incorporating IL-12 secretion capabilities was successfully designed and implemented in immune-cell models, enabling the generation of engineered cellular platforms for extracellular vesicle production.
Methodologies for extracellular vesicle production, purification and characterisation were established and refined through the evaluation of different isolation and engineering approaches. Functional assays and proof-of-concept loading experiments demonstrated the feasibility of using engineered extracellular vesicles as delivery platforms.
In parallel, in vitro and in vivo experimental platforms relevant to PDAC research were developed, including three-dimensional cellular models and orthotopic pancreatic tumour models in mice, which will support full evaluation of the proposed therapeutic strategy beyond the fellowship period.
As an additional research component, complementary molecular analyses were incorporated to identify biological pathways potentially relevant for future combinatorial immunotherapy approaches. These activities contributed to expanding the scientific scope of the project and generating new mechanistic hypotheses for future research activities.
Overall, the project enabled the establishment of robust technological and experimental workflows that provide the basis for continued development of this approach. Further results generated through continuation of these activities will be communicated through future scientific publications.
