AI Article Synopsis
- - Lipid nanoparticles (LNPs) can be engineered to improve cancer immunotherapy by enhancing their uptake by immune cells and boosting their activation.
- - A new screening method was developed to optimize the lipid components of LNPs for better delivery of tumor-antigen-encoding mRNA to dendritic cells, leading to stronger immune responses.
- - The study showed that the most effective antitumor response occurs when LNPs trigger strong activity in both T cells and NK cells, especially when combined with immune checkpoint inhibitors, highlighting the significance of customizing LNPs for better cancer vaccine performance.
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11162325 | PMC |
| http://dx.doi.org/10.1038/s41551-023-01131-0 | DOI Listing |
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