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An Inter‐Supplementary Biohybrid System Based on Natural Killer Cells for the Combinational Immunotherapy and Virotherapy of Cancer
Oncolytic adenoviruses (Ads) have gained great attention in cancer therapy because they cause direct cytolytic infection and indirectly induce antitumor immunity. However, their efficacy is compromised by host antiviral immune response, poor tumor delivery, and the immunosuppressive tumor microenvir...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805568/ https://www.ncbi.nlm.nih.gov/pubmed/34747156 http://dx.doi.org/10.1002/advs.202103470 |
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author | Ding, Li Gao, Qingqing Xu, Zhuobin Cai, Liangliang Chen, Sujuan Zhang, Xinyue Cao, Peng Chen, Gang |
author_facet | Ding, Li Gao, Qingqing Xu, Zhuobin Cai, Liangliang Chen, Sujuan Zhang, Xinyue Cao, Peng Chen, Gang |
author_sort | Ding, Li |
collection | PubMed |
description | Oncolytic adenoviruses (Ads) have gained great attention in cancer therapy because they cause direct cytolytic infection and indirectly induce antitumor immunity. However, their efficacy is compromised by host antiviral immune response, poor tumor delivery, and the immunosuppressive tumor microenvironment (TME). Here, a natural killer (NK) cell‐mediated Ad delivery system (Ad@NK) is generated by harnessing the merits of the two components for combinational immunotherapy and virotherapy of cancer. In this biohybrid system, NK cells with a tumor‐homing tropism act as bioreactors and shelters for the loading, protection, replication, amplification, and release of Ads, thereby leading to a highly efficient systemic tumor‐targeted delivery. As feedback, Ad infection offers NK cells an enhanced antitumor immunity by activating type I interferon signaling in a STAT4‐granzyme B‐dependent manner. Moreover, it is found that the Ad@NK system can relieve immunosuppression in the TME by promoting the maturation of dendritic cells and the polarization of macrophages to M1 phenotype. Both in vitro and in vivo data indicate the excellent antitumor and antimetastatic functions of Ad@NKs by destroying tumor cells, inducing immunogenic cell death, and immunomodulating TME. This work provides a clinical basis for improved oncolytic virotherapy in combination with NK cell therapy based on the inter‐supplementary biohybrid system. |
format | Online Article Text |
id | pubmed-8805568 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88055682022-02-04 An Inter‐Supplementary Biohybrid System Based on Natural Killer Cells for the Combinational Immunotherapy and Virotherapy of Cancer Ding, Li Gao, Qingqing Xu, Zhuobin Cai, Liangliang Chen, Sujuan Zhang, Xinyue Cao, Peng Chen, Gang Adv Sci (Weinh) Research Articles Oncolytic adenoviruses (Ads) have gained great attention in cancer therapy because they cause direct cytolytic infection and indirectly induce antitumor immunity. However, their efficacy is compromised by host antiviral immune response, poor tumor delivery, and the immunosuppressive tumor microenvironment (TME). Here, a natural killer (NK) cell‐mediated Ad delivery system (Ad@NK) is generated by harnessing the merits of the two components for combinational immunotherapy and virotherapy of cancer. In this biohybrid system, NK cells with a tumor‐homing tropism act as bioreactors and shelters for the loading, protection, replication, amplification, and release of Ads, thereby leading to a highly efficient systemic tumor‐targeted delivery. As feedback, Ad infection offers NK cells an enhanced antitumor immunity by activating type I interferon signaling in a STAT4‐granzyme B‐dependent manner. Moreover, it is found that the Ad@NK system can relieve immunosuppression in the TME by promoting the maturation of dendritic cells and the polarization of macrophages to M1 phenotype. Both in vitro and in vivo data indicate the excellent antitumor and antimetastatic functions of Ad@NKs by destroying tumor cells, inducing immunogenic cell death, and immunomodulating TME. This work provides a clinical basis for improved oncolytic virotherapy in combination with NK cell therapy based on the inter‐supplementary biohybrid system. John Wiley and Sons Inc. 2021-11-07 /pmc/articles/PMC8805568/ /pubmed/34747156 http://dx.doi.org/10.1002/advs.202103470 Text en © 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Ding, Li Gao, Qingqing Xu, Zhuobin Cai, Liangliang Chen, Sujuan Zhang, Xinyue Cao, Peng Chen, Gang An Inter‐Supplementary Biohybrid System Based on Natural Killer Cells for the Combinational Immunotherapy and Virotherapy of Cancer |
title | An Inter‐Supplementary Biohybrid System Based on Natural Killer Cells for the Combinational Immunotherapy and Virotherapy of Cancer |
title_full | An Inter‐Supplementary Biohybrid System Based on Natural Killer Cells for the Combinational Immunotherapy and Virotherapy of Cancer |
title_fullStr | An Inter‐Supplementary Biohybrid System Based on Natural Killer Cells for the Combinational Immunotherapy and Virotherapy of Cancer |
title_full_unstemmed | An Inter‐Supplementary Biohybrid System Based on Natural Killer Cells for the Combinational Immunotherapy and Virotherapy of Cancer |
title_short | An Inter‐Supplementary Biohybrid System Based on Natural Killer Cells for the Combinational Immunotherapy and Virotherapy of Cancer |
title_sort | inter‐supplementary biohybrid system based on natural killer cells for the combinational immunotherapy and virotherapy of cancer |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805568/ https://www.ncbi.nlm.nih.gov/pubmed/34747156 http://dx.doi.org/10.1002/advs.202103470 |
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