학술논문
Screening for lipid nanoparticles that modulate the immune activity of helper T cells towards enhanced antitumour activity.
Document Type
Academic Journal
Author
Zhu Y; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Ma J; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.; Shen R; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Lin J; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Li S; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Lu X; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.; Stelzel JL; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Kong J; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.; Cheng L; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Vuong I; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Yao ZC; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.; Wei C; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Korinetz NM; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.; Toh WH; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA.; Department of Biology, Johns Hopkins University, Baltimore, MD, USA.; Choy J; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.; Reynolds RA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.; Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, WA, USA.; Shears MJ; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.; Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, WA, USA.; Cho WJ; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.; Livingston NK; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Howard GP; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Hu Y; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Tzeng SY; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Zack DJ; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Green JJ; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center and the Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Zheng L; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center and the Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Doloff JC; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center and the Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Schneck JP; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Reddy SK; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.; Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Murphy SC; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA. murphysc@uw.edu.; Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, WA, USA. murphysc@uw.edu.; Department of Microbiology, University of Washington, Seattle, WA, USA. murphysc@uw.edu.; Mao HQ; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. hmao@jhu.edu.; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA. hmao@jhu.edu.; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. hmao@jhu.edu.; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA. hmao@jhu.edu.
Source
Publisher: Springer Nature Country of Publication: England NLM ID: 101696896 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2157-846X (Electronic) Linking ISSN: 2157846X NLM ISO Abbreviation: Nat Biomed Eng Subsets: MEDLINE
Subject
Language
English
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.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)