Screening for lipid nanoparticles that modulate the immune activity of helper T cells towards enhanced antitumour activity
Menée in vitro et à l'aide d'un modèle murin de mélanome, cette étude met en évidence l'intérêt d'une méthode de criblage de nanoparticules lipidiques pour optimiser la composition de ces dernières, améliorer la délivrance aux cellules dendritiques d'ARNs messagers codant pour des antigènes tumoraux et augmenter ainsi l'activité antitumorale des lymphocytes T auxiliaires
Lipid nanoparticles (LNPs) can be designed to potentiate cancer immunotherapy by promoting their uptake by antigen-presenting cells, stimulating the maturation of these cells and modulating the activity of adjuvants. Here we report an LNP-screening method for the optimization of the type of helper lipid and of lipid-component ratios to enhance the delivery of tumour-antigen-encoding mRNA to dendritic cells and their immune-activation profile towards enhanced antitumour activity. The method involves screening for LNPs that enhance the maturation of bone-marrow-derived dendritic cells and antigen presentation in vitro, followed by assessing immune activation and tumour-growth suppression in a mouse model of melanoma after subcutaneous or intramuscular delivery of the LNPs. We found that the most potent antitumour activity, especially when combined with immune checkpoint inhibitors, resulted from a coordinated attack by T cells and NK cells, triggered by LNPs that elicited strong immune activity in both type-1 and type-2 T helper cells. Our findings highlight the importance of optimizing the LNP composition of mRNA-based cancer vaccines to tailor antigen-specific immune-activation profiles.
Nature Biomedical Engineering , résumé, 2023