Single-dose injectable nanovaccine-in-hydrogel for robust immunotherapy of large tumors with abscopal effect
Menée in vitro puis à l'aide de modèles murins de tumeurs faiblement immunogènes et d'un modèle murin de glioblastome orthotopique, cette étude met en évidence l'intérêt thérapeutique de l'injection intratumorale d'un hydrogel chargé en anticorps anti-points de contrôle immunitaires et en nanoparticules comportant des agonistes des récepteurs TLR7/8/9 et de la protéine STING
Current cancer immunotherapy [e.g., immune checkpoint blockade (ICB)] only benefits small subsets of patients, largely due to immunosuppressive tumor microenvironment (TME). In situ tumor vaccination can reduce TME immunosuppression and thereby improve cancer immunotherapy. Here, we present single-dose injectable (nanovaccines + ICBs)-in-hydrogel (NvIH) for robust immunotherapy of large tumors with abscopal effect. NvIH is thermo-responsive hydrogel co-encapsulated with ICB antibodies and novel polymeric nanoparticles loaded with three immunostimulatory agonists for Toll-like receptors 7/8/9 (TLR7/8/9) and stimulator of interferon genes (STING). Upon in situ tumor vaccination, NvIH undergoes rapid sol-to-gel transformation, prolongs tumor retention, sustains the release of immunotherapeutics, and reduces acute systemic inflammation. In multiple poorly immunogenic tumor models, single-dose NvIH reduces multitier TME immunosuppression, elicits potent TME and systemic innate and adaptive antitumor immunity with memory, and regresses both local (vaccinated) and distant large tumors with abscopal effect, including distant orthotopic glioblastoma. Overall, NvIH holds great potential for tumor immunotherapy. Nanoparticle-in-hydrogel composites were developed to co-deliver immunotherapeutic cocktails to treat large tumor, near and far.
Science Advances 2023