Nanoparticle-enhanced chemo-immunotherapy to trigger robust antitumor immunity
Jingjing Liang, Huifang Wang, Huifang Wang, Wenxiu Ding, Jianxiang Huang, Xuefei Zhou, Huiyang Wang, Huiyang Wang, Xue Dong, Guangyao Li, Enguo Chen, Fei Zhou, Hongjie Fan, Jingya Xia, Bo Shen, Da Cai, Pengxun Lan, Hanliang Jiang, Jun Ling, Zhen Cheng, Xiangrui Liu, Jihong Sun
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.