Nanoparticle-enhanced chemo-immunotherapy to trigger robust antitumor immunity

• Published in: Science advances Vol. 6; no. 35; p. eabc3646
• Main Authors: Liang, Jingjing, Wang, Huifang, Ding, Wenxiu, Huang, Jianxiang, Zhou, Xuefei, Wang, Huiyang, Dong, Xue, Li, Guangyao, Chen, Enguo, Zhou, Fei, Fan, Hongjie, Xia, Jingya, Shen, Bo, Cai, Da, Lan, Pengxun, Jiang, Hanliang, Ling, Jun, Cheng, Zhen, Liu, Xiangrui, Sun, Jihong
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 01.08.2020
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Cancer; Immunologic Factors; Immunotherapy; Materials Science; Mice; Nanoparticles; Neoplasms - drug therapy; SciAdv r-articles; Tumor Microenvironment
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.abc3646

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.