Engineering a Smart Agent for Enhanced Immunotherapy Effect by Simultaneously Blocking PD‐L1 and CTLA‐4
Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single‐agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@1...
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| Published in: | Advanced science Vol. 8; no. 20; pp. e2102500 - n/a |
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| Main Authors: | , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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John Wiley & Sons, Inc
01.10.2021
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| ISSN: | 2198-3844, 2198-3844 |
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| Abstract | Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single‐agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19F‐ZIF‐8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein, which can bind to both PD‐L1 and CTLA‐4 effectively. ZIF‐8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19F‐ZIF‐8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy.
A novel smart agent is engineered by coating a tumor microenvironment responsive ZIF‐8 on the novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein to overcome the higher costs and greater side effects of single‐agent immunotherapies. |
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| AbstractList | Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single-agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19 F-ZIF-8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD-L1/CTLA-4 bispecific single-domain antibody-Fc fusion protein, which can bind to both PD-L1 and CTLA-4 effectively. ZIF-8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19 F-ZIF-8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy.Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single-agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19 F-ZIF-8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD-L1/CTLA-4 bispecific single-domain antibody-Fc fusion protein, which can bind to both PD-L1 and CTLA-4 effectively. ZIF-8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19 F-ZIF-8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy. Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single‐agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19F‐ZIF‐8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein, which can bind to both PD‐L1 and CTLA‐4 effectively. ZIF‐8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19F‐ZIF‐8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy. Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single‐agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19F‐ZIF‐8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein, which can bind to both PD‐L1 and CTLA‐4 effectively. ZIF‐8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19F‐ZIF‐8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy. A novel smart agent is engineered by coating a tumor microenvironment responsive ZIF‐8 on the novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein to overcome the higher costs and greater side effects of single‐agent immunotherapies. Abstract Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single‐agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19F‐ZIF‐8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein, which can bind to both PD‐L1 and CTLA‐4 effectively. ZIF‐8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19F‐ZIF‐8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy. Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single‐agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@ 19 F‐ZIF‐8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein, which can bind to both PD‐L1 and CTLA‐4 effectively. ZIF‐8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@ 19 F‐ZIF‐8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy. Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single‐agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19F‐ZIF‐8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein, which can bind to both PD‐L1 and CTLA‐4 effectively. ZIF‐8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19F‐ZIF‐8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy. A novel smart agent is engineered by coating a tumor microenvironment responsive ZIF‐8 on the novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein to overcome the higher costs and greater side effects of single‐agent immunotherapies. Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single-agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@ F-ZIF-8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD-L1/CTLA-4 bispecific single-domain antibody-Fc fusion protein, which can bind to both PD-L1 and CTLA-4 effectively. ZIF-8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@ F-ZIF-8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy. |
| Author | Tian, Qiwei Xu, Xiaoping Zhang, Le Song, Shaoli Zhang, Jianping Jiang, Chunjuan Qi, Ming He, Simin |
| AuthorAffiliation | 3 Shanghai Engineering Research Center of Molecular Imaging Probes Shanghai 200032 China 2 Center for Biomedical Imaging Fudan University Shanghai 200032 China 5 Shanghai Key Laboratory of Molecular Imaging Shanghai University of Medicine and Health Sciences Shanghai 201318 China 4 Department of Research and Development Shanghai Proton and Heavy Ion Center Shanghai 201321 China 1 Department of Nuclear Medicine Fudan University Shanghai Cancer Center Shanghai 200032 China |
| AuthorAffiliation_xml | – name: 1 Department of Nuclear Medicine Fudan University Shanghai Cancer Center Shanghai 200032 China – name: 4 Department of Research and Development Shanghai Proton and Heavy Ion Center Shanghai 201321 China – name: 5 Shanghai Key Laboratory of Molecular Imaging Shanghai University of Medicine and Health Sciences Shanghai 201318 China – name: 2 Center for Biomedical Imaging Fudan University Shanghai 200032 China – name: 3 Shanghai Engineering Research Center of Molecular Imaging Probes Shanghai 200032 China |
| Author_xml | – sequence: 1 givenname: Chunjuan surname: Jiang fullname: Jiang, Chunjuan organization: Shanghai Engineering Research Center of Molecular Imaging Probes – sequence: 2 givenname: Le surname: Zhang fullname: Zhang, Le organization: Shanghai Proton and Heavy Ion Center – sequence: 3 givenname: Xiaoping surname: Xu fullname: Xu, Xiaoping organization: Shanghai Engineering Research Center of Molecular Imaging Probes – sequence: 4 givenname: Ming surname: Qi fullname: Qi, Ming organization: Shanghai Engineering Research Center of Molecular Imaging Probes – sequence: 5 givenname: Jianping surname: Zhang fullname: Zhang, Jianping organization: Shanghai Engineering Research Center of Molecular Imaging Probes – sequence: 6 givenname: Simin surname: He fullname: He, Simin organization: Shanghai Engineering Research Center of Molecular Imaging Probes – sequence: 7 givenname: Qiwei surname: Tian fullname: Tian, Qiwei email: tianqw@sumhs.edu.cn organization: Shanghai University of Medicine and Health Sciences – sequence: 8 givenname: Shaoli orcidid: 0000-0003-2544-7522 surname: Song fullname: Song, Shaoli email: shaoli-song@163.com organization: Shanghai Proton and Heavy Ion Center |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34473430$$D View this record in MEDLINE/PubMed |
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| Title | Engineering a Smart Agent for Enhanced Immunotherapy Effect by Simultaneously Blocking PD‐L1 and CTLA‐4 |
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