Impact Factor:16.806
DOI number:10.1002/advs.202103470
Journal:Advanced Science
Key Words: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.
Abstract: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.
First Author:Ding Li
Indexed by:研究报告
Document Code:202103470
Discipline:Medicine
Document Type:SCI
Volume:9
Issue:2
Translation or Not:no
Date of Publication:2021-11-07
Included Journals:SCI