Personalized Tumor RNA Loaded Lipid-Nanoparticles Prime the Systemic and Intratumoral Milieu for Response to Cancer Immunotherapy
Elias Sayour(Allen Institute for Brain Science), Adam Grippin(Allen Institute for Brain Science), Gabriel De Leon(Allen Institute for Brain Science), Brian Stover(Allen Institute for Brain Science), Maryam Rahman(Allen Institute for Brain Science), Aida Karachi(Allen Institute for Brain Science), Brandon Wummer(Allen Institute for Brain Science), Ginger Moore(Allen Institute for Brain Science), Paul Castillo‐Caro(Allen Institute for Brain Science), Kristianna M. Fredenburg(University of Florida), Matthew R. Sarkisian(Allen Institute for Brain Science), Jianping Huang(Allen Institute for Brain Science), Loic P. Deleyrolle(Allen Institute for Brain Science), Bikash Sahay(University of Florida), Sheila Carrera‐Justiz(University of Florida), Héctor R. Méndez‐Gómez(Allen Institute for Brain Science), Duane A. Mitchell(Allen Institute for Brain Science)
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Abstract
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.
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