RT Journal Article
SR Electronic
T1 Nanoparticle-enhanced chemo-immunotherapy to trigger robust antitumor immunity
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eabc3646
DO 10.1126/sciadv.abc3646
VO 6
IS 35
A1 Liang, Jingjing
A1 Wang, Huifang
A1 Ding, Wenxiu
A1 Huang, Jianxiang
A1 Zhou, Xuefei
A1 Wang, Huiyang
A1 Dong, Xue
A1 Li, Guangyao
A1 Chen, Enguo
A1 Zhou, Fei
A1 Fan, Hongjie
A1 Xia, Jingya
A1 Shen, Bo
A1 Cai, Da
A1 Lan, Pengxun
A1 Jiang, Hanliang
A1 Ling, Jun
A1 Cheng, Zhen
A1 Liu, Xiangrui
A1 Sun, Jihong
YR 2020
UL http://advances.sciencemag.org/content/6/35/eabc3646.abstract
AB 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.