Dendritic Cell-Activating Magnetic Nanoparticles Enable Early Prediction of Antitumor Response with Magnetic Resonance Imaging

ACS Nano. 2019 Dec 24;13(12):13884-13898. doi: 10.1021/acsnano.9b05037. Epub 2019 Dec 2.

Abstract

Cancer vaccines initiate antitumor responses in a subset of patients, but the lack of clinically meaningful biomarkers to predict treatment response limits their development. Here, we design multifunctional RNA-loaded magnetic liposomes to initiate potent antitumor immunity and function as an early biomarker of treatment response. These particles activate dendritic cells (DCs) more effectively than electroporation, leading to superior inhibition of tumor growth in treatment models. Inclusion of iron oxide enhances DC transfection and enables tracking of DC migration with magnetic resonance imaging (MRI). We show that T2*-weighted MRI intensity in lymph nodes is a strong correlation of DC trafficking and is an early predictor of antitumor response. In preclinical tumor models, MRI-predicted "responders" identified 2 days after vaccination had significantly smaller tumors 2-5 weeks after treatment and lived 73% longer than MRI-predicted "nonresponders". These studies therefore provide a simple, scalable nanoparticle formulation to generate robust antitumor immune responses and predict individual treatment outcome with MRI.

Keywords: RNA; RNA-lipoplex; biomarker; cancer; cancer immunotherapy; dendritic cells; iron oxide; liposome; nanoparticle; vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Biomarkers, Tumor / metabolism
  • Cancer Vaccines / immunology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Tracking
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism*
  • Electroporation
  • Ferric Compounds / chemistry
  • Magnetic Resonance Imaging*
  • Magnetite Nanoparticles / chemistry*
  • Magnetite Nanoparticles / ultrastructure
  • Mice, Inbred C57BL
  • Transfection

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Cancer Vaccines
  • Ferric Compounds
  • Magnetite Nanoparticles
  • ferric oxide