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Screening for lipid nanoparticles that modulate the immune activity of helper T cells towards enhanced antitumour activity.
Zhu, Yining; Ma, Jingyao; Shen, Ruochen; Lin, Jinghan; Li, Shuyi; Lu, Xiaoya; Stelzel, Jessica L; Kong, Jiayuan; Cheng, Leonardo; Vuong, Ivan; Yao, Zhi-Cheng; Wei, Christine; Korinetz, Nicole M; Toh, Wu Han; Choy, Joseph; Reynolds, Rebekah A; Shears, Melanie J; Cho, Won June; Livingston, Natalie K; Howard, Gregory P; Hu, Yizong; Tzeng, Stephany Y; Zack, Donald J; Green, Jordan J; Zheng, Lei; Doloff, Joshua C; Schneck, Jonathan P; Reddy, Sashank K; Murphy, Sean C; Mao, Hai-Quan.
Affiliation
  • Zhu Y; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Ma J; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
  • Shen R; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Lin J; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
  • Li S; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Lu X; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • Stelzel JL; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • Kong J; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Cheng L; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
  • Vuong I; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Yao ZC; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Wei C; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
  • Korinetz NM; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Toh WH; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
  • Choy J; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Reynolds RA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Shears MJ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Cho WJ; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
  • Livingston NK; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Howard GP; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • Hu Y; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Tzeng SY; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
  • Zack DJ; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Green JJ; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
  • Zheng L; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Doloff JC; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • Schneck JP; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Reddy SK; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
  • Murphy SC; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Mao HQ; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nat Biomed Eng ; 2023 Dec 11.
Article in En | MEDLINE | ID: mdl-38082180
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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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Nat Biomed Eng Year: 2023 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Nat Biomed Eng Year: 2023 Document type: Article Affiliation country: United States