Nanoparticle-enhanced chemo-immunotherapy to trigger robust antitumor immunity
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 combin...
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| Published in | Science advances Vol. 6; no. 35; p. eabc3646 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Association for the Advancement of Science
01.08.2020
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| Subjects | |
| Online Access | Get full text |
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| 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. |
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| AbstractList | 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. Stimuli-responsive nano-immunochemotherapy modulates the tumor microenvironment to enhance antitumor immunity. 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. |
| Author | Ling, Jun Xia, Jingya Fan, Hongjie Li, Guangyao Huang, Jianxiang Sun, Jihong Chen, Enguo Wang, Huifang Zhou, Xuefei Dong, Xue Jiang, Hanliang Lan, Pengxun Cheng, Zhen Liu, Xiangrui Shen, Bo Zhou, Fei Ding, Wenxiu Wang, Huiyang Liang, Jingjing Cai, Da |
| Author_xml | – sequence: 1 givenname: Jingjing orcidid: 0000-0002-6766-4747 surname: Liang fullname: Liang, Jingjing organization: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China – sequence: 2 givenname: Huifang orcidid: 0000-0003-4367-2416 surname: Wang fullname: Wang, Huifang organization: Key Laboratory of Biomass Chemical Engineering of Ministry of Education and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China – sequence: 3 givenname: Wenxiu orcidid: 0000-0001-8853-2068 surname: Ding fullname: Ding, Wenxiu organization: Second Clinical Medical College, Zhejiang Chinese Medical University, Quzhou 310053, China – sequence: 4 givenname: Jianxiang orcidid: 0000-0003-1394-2147 surname: Huang fullname: Huang, Jianxiang organization: Key Laboratory of Biomass Chemical Engineering of Ministry of Education and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China – sequence: 5 givenname: Xuefei orcidid: 0000-0003-2978-4315 surname: Zhou fullname: Zhou, Xuefei organization: Key Laboratory of Biomass Chemical Engineering of Ministry of Education and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China – sequence: 6 givenname: Huiyang orcidid: 0000-0001-7709-8155 surname: Wang fullname: Wang, Huiyang organization: Second Clinical Medical College, Zhejiang Chinese Medical University, Quzhou 310053, China – sequence: 7 givenname: Xue orcidid: 0000-0001-5243-6453 surname: Dong fullname: Dong, Xue organization: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China – sequence: 8 givenname: Guangyao orcidid: 0000-0002-1336-3666 surname: Li fullname: Li, Guangyao organization: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China – sequence: 9 givenname: Enguo orcidid: 0000-0003-2338-8610 surname: Chen fullname: Chen, Enguo organization: Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China – sequence: 10 givenname: Fei orcidid: 0000-0002-6533-5181 surname: Zhou fullname: Zhou, Fei organization: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China – sequence: 11 givenname: Hongjie orcidid: 0000-0002-0211-2888 surname: Fan fullname: Fan, Hongjie organization: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China – sequence: 12 givenname: Jingya orcidid: 0000-0002-0232-7053 surname: Xia fullname: Xia, Jingya organization: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China – sequence: 13 givenname: Bo orcidid: 0000-0002-7826-0684 surname: Shen fullname: Shen, Bo organization: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China – sequence: 14 givenname: Da orcidid: 0000-0002-3361-3730 surname: Cai fullname: Cai, Da organization: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China – sequence: 15 givenname: Pengxun orcidid: 0000-0002-3889-5976 surname: Lan fullname: Lan, Pengxun organization: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China – sequence: 16 givenname: Hanliang orcidid: 0000-0003-0902-882X surname: Jiang fullname: Jiang, Hanliang organization: Pulmonary and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China – sequence: 17 givenname: Jun orcidid: 0000-0002-0365-1381 surname: Ling fullname: Ling, Jun organization: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China – sequence: 18 givenname: Zhen orcidid: 0000-0001-8177-9463 surname: Cheng fullname: Cheng, Zhen organization: Molecular Imaging Program at Stanford (MIPS) and Bio-X Program, Stanford University Medical Center, Stanford, CA 94305, USA – sequence: 19 givenname: Xiangrui orcidid: 0000-0003-4960-5847 surname: Liu fullname: Liu, Xiangrui organization: Key Laboratory of Biomass Chemical Engineering of Ministry of Education and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China – sequence: 20 givenname: Jihong orcidid: 0000-0001-5362-2450 surname: Sun fullname: Sun, Jihong organization: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32923651$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 2020 The Authors |
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