Journal
SCIENCE ADVANCES
Volume 6, Issue 35, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abc3646
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Funding
- National Key Research and Development Program of China [2016YFA0100900]
- National Natural Science Foundation of China [81871403, 81901595, 51773176, 21975218]
- Key Research and Development Program of Zhejiang Province [2019C03014]
- National Postdoctoral Science Foundation of China [2018M640564, 2019T120524]
- Zhejiang Postdoctoral Selective Foundation [zj20180121]
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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.
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