Personalized Tumor RNA Loaded Lipid-Nanoparticles Prime the Systemic and Intratumoral Milieu for Response to Cancer Immunotherapy

著者: Elias Sayour, Adam Grippin, Gabriel De Leon, Brian Stover, Maryam Rahman, Aida Karachi, Brandon Wummer, Ginger Moore, Paul Castillo‐Caro, Kristianna M. Fredenburg, Matthew R. Sarkisian, Jianping Huang, Loic P. Deleyrolle, Bikash Sahay, Sheila Carrera‐Justiz, Héctor R. Méndez‐Gómez, Duane A. Mitchell - Nano Letters 2018 被引用: 113

cells and mediates synergistic antitumor efficacy in settings where ICIs alone do not confer therapeutic benefit. These synergistic effects are mediated by type I interferon released from plasmacytoid dendritic cells (pDCs). In translational studies, personalized mRNA-NPs were safe and active in a client-owned canine with a spontaneous malignant glioma. In summary, we demonstrate widespread immune activation from tumor loaded RNA-NPs concomitant with inducible PD-L1 expression that can be therapeutically exploited. While immunotherapy remains effective for only a subset of cancer patients, combination therapy with systemic immunomodulating RNA-NPs may broaden its therapeutic potency.