Nanoparticle-enhanced chemo-immunotherapy to trigger robust antitumor immunity
Open Access
- 28 August 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 6 (35), eabc3646
- https://doi.org/10.1126/sciadv.abc3646
Abstract
Mounting evidence suggests that immunotherapies are a promising new class of anticancer therapies. However, the immunosuppressive tumor microenvironment (TME), poor immunogenicity, and off-target toxicity hinder the broader implementation of immunotherapies. Here, we describe a novel strategy combining chemotherapy and immunotherapy to modulate the TME by systemically and concurrently delivering the chemotherapeutic agent SN38 (7-ethyl-10-hydroxycamptothecin) and the STING agonist DMXAA (5,6-dimethylxanthenone-4-acetic acid) into tumors using triblock copolymer nanoparticles, named PS3D1@DMXAA, which enhances antigen cross-presentation and induces the conversion of the immunosuppressive TME to immunogenic TME through the newly found synergistic function between SN38 and STING activation. PS3D1@DMXAA thus shows potent therapeutic efficacy in three mice tumor models and elicits remarkable therapeutic benefit when combined with anti–PD-1 therapy. Our engineered nanosystem offers a rational design of an effective immunotherapy combination regimen to convert uninflamed “cold” tumors into “hot” tumors, addressing the major challenges immunotherapies faced.Funding Information
- National Natural Science Foundation of China (81871403)
- National Natural Science Foundation of China (81901595)
- National Natural Science Foundation of China (51773176)
- National Natural Science Foundation of China (21975218)
- National Key Research and Development Program of China Stem Cell and Translational Research (2016YFA0100900)
- Key Research and Development Program of Zhejiang Province (2019C03014)
- National Postdoctoral Science Foundation of China Grants (2018M640564)
- National Postdoctoral Science Foundation of China Grants (2019T120524)
- Zhejiang Postdoctoral Selective Foundation (zj20180121)
This publication has 41 references indexed in Scilit:
- DMXAA Causes Tumor Site-Specific Vascular Disruption in Murine Non-Small Cell Lung Cancer, and like the Endogenous Non-Canonical Cyclic Dinucleotide STING Agonist, 2′3′-cGAMP, Induces M2 Macrophage RepolarizationPLOS ONE, 2014
- Tumour-infiltrating CD4+ and CD8+ lymphocytes as predictors of clinical outcome in gliomaBritish Journal of Cancer, 2014
- Preparation of a Camptothecin Prodrug with Glutathione‐Responsive Disulfide Linker for Anticancer Drug DeliveryChemistry – An Asian Journal, 2013
- Up-Regulation of PD-L1, IDO, and T regs in the Melanoma Tumor Microenvironment Is Driven by CD8 + T CellsScience Translational Medicine, 2013
- Combined treatment of human colorectal tumor cell lines with chemotherapeutic agents and ionizing irradiation canin vitroinduce tumor cell death forms with immunogenic potentialJournal of Immunotoxicology, 2012
- The role of non-covalent interactions in anticancer drug loading and kinetic stability of polymeric micellesBiomaterials, 2012
- Chemotherapy Induces Intratumoral Expression of Chemokines in Cutaneous Melanoma, Favoring T-cell Infiltration and Tumor ControlCancer Research, 2011
- Intracellular glutathione redox status in human dendritic cells regulates IL-27 production and T-cell polarizationAllergy, 2011
- The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapyImmunological Reviews, 2007
- Development and testing of a general amber force fieldJournal of Computational Chemistry, 2004