| Literature DB >> 31730332 |
Adam J Grippin1,2, Brandon Wummer1, Tyler Wildes1, Kyle Dyson1, Vrunda Trivedi1, Changlin Yang1, Mathew Sebastian1, Hector R Mendez-Gomez1, Suraj Padala1, Mackenzie Grubb2, Matthew Fillingim1, Adam Monsalve2, Elias J Sayour1, Jon Dobson2,3, Duane A Mitchell1.
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.Entities:
Keywords: RNA; RNA-lipoplex; biomarker; cancer; cancer immunotherapy; dendritic cells; iron oxide; liposome; nanoparticle; vaccine
Year: 2019 PMID: 31730332 DOI: 10.1021/acsnano.9b05037
Source DB: PubMed Journal: ACS Nano ISSN: 1936-0851 Impact factor: 15.881