Description du projet
Une nouvelle immunothérapie grâce aux lymphocytes B
Les lymphocytes B remplissent différentes fonctions immunologiques, notamment la production d’anticorps et la présentation antigénique. De nouvelles données indiquent que ces cellules créent également des niches, appelées structures lymphoïdes tertiaires (SLT) associées aux lymphocytes B, qui favorisent la réponse immunitaire. Le rôle des SLT dans le cancer commence seulement à être compris, et sa compréhension nécessite une meilleure connaissance de la composition cellulaire et spatiale. Financé par le Conseil européen de la recherche, le projet BeaT-IT cherche à déterminer les facteurs qui stimulent les lymphocytes B et induisent les SLT. Les chercheurs auront recours à de nouveaux biomatériaux polymères et testeront différents agents et cellules afin de déterminer leur capacité à stimuler la formation de SLT. Ces matériaux pourront ensuite être combinés à l’immunothérapie ou à la chimiothérapie dans le cadre d’une stratégie anticancéreuse synergique.
Objectif
Recent clinical evidence points to a potential new direction in immuno-oncology: utilizing B cells and B cell-associated tertiary lymphoid structures (TLS). B cells display diverse immunological actions, including antibody production, antigen presentation, cytokine secretion and TLS induction. They have a dual role: they can initiate and reinforce anti-cancer immunity but B cells can also acquire regulatory phenotypes. To open up a new immunotherapeutic paradigm, I aim to understand how to optimally activate B cells, using nano-/biomaterials which load and precisely release a variety of agents to stimulate B cells and to suppress B cell regulatory phenotypes. Furthermore, I will manufacture porous scaffolds based on injectable microgels or via 3D printing with microgel fibers to induce TLS formation. The scaffolds with tunable porosity will allow B cells and other immune/stromal cells to infiltrate, arrange and expand, and soluble factors to diffuse. Moreover, the scaffolds can be easily functionalized with different chemical cues to stimulate B cells for TLS formation, such as CXC-chemokine ligand 13 and interleukin-7. This will help us understand TLS induction. Importantly, I will use ex vivo engineered TLS to study what microenvironmental factors influence their functionality. Subsequently, in vivo formation of B cell-associated TLS will be induced by the scaffolds. B cell activation and TLS induction will be combined for tumor therapy, and potential abscopal effect of the treatment to address metastases will be studied. The materials will be further combined with checkpoint inhibitors and chemotherapy to reach synergism. In addition, the new therapeutic strategies will be tested in patient-derived tumors established in humanized mice. BeaT-IT aims to understand optimal B cell activation and TLS formation with nano-/biomaterials to establish a new direction in immuno-oncology, which is anticipated to realize an upcoming breakthrough in cancer immunotherapy.
Champ scientifique
CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN.
CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN.
- engineering and technologymaterials engineeringfibers
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicineimmunologyimmunotherapy
- engineering and technologymechanical engineeringmanufacturing engineeringadditive manufacturing
- engineering and technologyindustrial biotechnologybiomaterials
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
HORIZON-AG - HORIZON Action Grant Budget-BasedInstitution d’accueil
52074 Aachen
Allemagne