Lipid Nanoparticles of Type-A CpG D35 Suppress Tumor Growth by Changing Tumor Immune-microenvironment and Activate CD8 T Cells in Mice


Authors: L. Munakata, Y. Tanimoto, A. Osa, J. Meng, Y. Haseda, Y. Naito, H. Machiyama, A. Kumanogoh, D. Omata, K. Maruyama, Y. Yoshioka, Y. Okada, S. Koyama, R. Suzuki, and T. Aoshi

Journal: Journal of Controlled Release

DOI: 10.1016/j.jconrel.2019.09.011

Publication - Abstract

November 30, 2019

Oncology Nucleic Acid Lipid Nanoparticles mRNA

Abstract


Type-A CpG oligodeoxynucleotides (ODNs), which have a natural phosphodiester backbone, is one of the highest IFN-α inducer from plasmacytoid dendritic cells (pDC) via Toll-like receptor 9 (TLR9)-dependent signaling. However, the in vivo application of Type-A CpG has been limited because the rapid degradation in vivo results in relatively weak biological effect compared to other Type-B, -C, and -P CpG ODNs, which have nuclease-resistant phosphorothioate backbones. To overcome this limitation, we developed lipid nanoparticles formulation containing a Type-A CpG ODN, D35 (D35LNP). When tested in a mouse tumor model, intratumoral and intravenous D35LNP administration significantly suppressed tumor growth in a CD8 T cell-dependent manner, whereas original D35 showed no efficacy. Tumor suppression was associated with Th1-related gene induction and activation of CD8 T cells in the tumor. The combination of D35LNP and an anti-PD-1 antibody increased the therapeutic efficacy. Importantly, the therapeutic schedule and dose of intravenous D35LNP did not induce apparent liver toxicity. These results suggested that D35LNP is a safe and effective immunostimulatory drug formulation for cancer immunotherapy.

limit search to this category
Advanced Search

Advanced Search

close
  • Publications
  • Application Notes
  • Posters
  • Workshops
  • Videos & Webinars
  • Articles
Search

Browse by Category

  • Application
    • Diagnostic and Imaging
    • Genetic Medicine
    • Hematology
    • Metabolic Disorders
    • Neuroscience
    • Oncology
    • Skeletal Disorders
    • Targeted Drug Delivery
    • Vaccines
    • Other Applications
    • Cell therapy
  • Formulation
    • Liposomes
    • Nucleic Acid Lipid Nanoparticles
    • Polymeric Nanoparticles
    • Other Formulations
  • Payload
    • DNA
    • microRNA
    • mRNA
    • siRNA
    • Small Molecule Drugs
    • Other Payloads


related content

Publication - Abstract

Jan 08, 2018
Scientific Reports

High Content Image Analysis Reveals Function of miR-124 Upstream of Vimentin in Regulating Motor Neuron Mitochondria

T. Yardeni, R. Fine, Y. Joshi, T. Gradus-Pery, N. Kozer, I. Reichenstein, E. Yanowski, S. Nevo, H. Weiss-Tishler, M. Eisenberg-Bord, T. Shalit, A. Plotnikov, H.M. Barr, E. Perlson and E. Hornstein

Other Payloads microRNA Nucleic Acid Lipid Nanoparticles

microRNAs (miRNAs) are critical for neuronal function and their dysregulation is repeatedly observed in neurodegenerative diseases. Here, we implemented high content image analysis for investigating the impact of several miRNAs in mouse primary mot...

Read More


Publication - Abstract

Jan 29, 2019
Pharmaceutics

Advances of Non-Ionic Surfactant Vesicles (Niosomes) and Their Application in Drug Delivery

X. Ge, M. Wei, S. He and W-E. Yuan

Small Molecule Drugs Other Formulations Other Payloads
Non-Ionic surfactant based vesicles, also known as niosomes, have attracted much attention in pharmaceutical fields due to their excellent behavior in encapsulating both hydrophilic and hydrophobic agents. In recent years, it has been discovered that these vesicles can improve th...
Read More


Sign Up and Stay Informed
Sign up today to automatically receive new Cytiva, formerly Precision NanoSystems application notes, conference posters, relevant science publications, and webinar invites.
Sign Up