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Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy

The clinical outcomes of cancer nanovaccine have been largely impeded owing to the low antigen-specific T cell response rate and acquired resistance caused by the immunosuppressive tumor microenvironment (TME). Here, we reported a tumor acidity-responsive nanovaccine to remodel the immunosuppressive...

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Autores principales: Xie, Xiaoxue, Feng, Yi, Zhang, Hanxi, Su, Qingqing, Song, Ting, Yang, Geng, Li, Ningxi, Wei, Xiaodan, Li, Tingting, Qin, Xiang, Li, Shun, Wu, Chunhui, Zhang, Xiaojuan, Wang, Guixue, Liu, Yiyao, Yang, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8958467/
https://www.ncbi.nlm.nih.gov/pubmed/35386322
http://dx.doi.org/10.1016/j.bioactmat.2022.03.008
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author Xie, Xiaoxue
Feng, Yi
Zhang, Hanxi
Su, Qingqing
Song, Ting
Yang, Geng
Li, Ningxi
Wei, Xiaodan
Li, Tingting
Qin, Xiang
Li, Shun
Wu, Chunhui
Zhang, Xiaojuan
Wang, Guixue
Liu, Yiyao
Yang, Hong
author_facet Xie, Xiaoxue
Feng, Yi
Zhang, Hanxi
Su, Qingqing
Song, Ting
Yang, Geng
Li, Ningxi
Wei, Xiaodan
Li, Tingting
Qin, Xiang
Li, Shun
Wu, Chunhui
Zhang, Xiaojuan
Wang, Guixue
Liu, Yiyao
Yang, Hong
author_sort Xie, Xiaoxue
collection PubMed
description The clinical outcomes of cancer nanovaccine have been largely impeded owing to the low antigen-specific T cell response rate and acquired resistance caused by the immunosuppressive tumor microenvironment (TME). Here, we reported a tumor acidity-responsive nanovaccine to remodel the immunosuppressive TME and expand the recruitment of tumor infiltrating lymphocytes (TILs) using hybrid micelles (HM), which encapsulated colony stimulating factor 1 receptor (CSF1-R) inhibitor BLZ-945 and indoleamine 2,3-dioxygenase (IDO) inhibitor NLG-919 in its core and displayed a model antigen ovalbumin (OVA) on its surface (denoted as BN@HM-OVA). The bioactive nanovaccine is coated with a polyethylene glycol (PEG) shell for extending nanoparticle circulation. The shell can be shed in response to the weakly acidic tumor microenvironment. The decrease in size and the increase in positive charge may cause the deep tumor penetration of drugs. We demonstrated that the bioactive nanovaccine dramatically enhance antigen presentation by dendritic cells (DCs) and drugs transportation into M1-like tumor-associated macrophages (TAMs) and tumor cells via size reduction and increasing positive charge caused by the weakly acidic TME. Such bioactive nanovaccine could remodel the immunosuppressive TME into an effector T cells favorable environment, leading to tumor growth inhibition in prophylactic and therapeutic E.G7-OVA tumor models. Furthermore, combining the bioactive nanovaccine with simultaneous anti-PD-1 antibody treatment leads to a long-term tumor inhibition, based on the optimal timing and sequence of PD-1 blockade against T cell receptor. This research provides a new strategy for the development of efficient cancer immunotherapy.
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spelling pubmed-89584672022-04-05 Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy Xie, Xiaoxue Feng, Yi Zhang, Hanxi Su, Qingqing Song, Ting Yang, Geng Li, Ningxi Wei, Xiaodan Li, Tingting Qin, Xiang Li, Shun Wu, Chunhui Zhang, Xiaojuan Wang, Guixue Liu, Yiyao Yang, Hong Bioact Mater Article The clinical outcomes of cancer nanovaccine have been largely impeded owing to the low antigen-specific T cell response rate and acquired resistance caused by the immunosuppressive tumor microenvironment (TME). Here, we reported a tumor acidity-responsive nanovaccine to remodel the immunosuppressive TME and expand the recruitment of tumor infiltrating lymphocytes (TILs) using hybrid micelles (HM), which encapsulated colony stimulating factor 1 receptor (CSF1-R) inhibitor BLZ-945 and indoleamine 2,3-dioxygenase (IDO) inhibitor NLG-919 in its core and displayed a model antigen ovalbumin (OVA) on its surface (denoted as BN@HM-OVA). The bioactive nanovaccine is coated with a polyethylene glycol (PEG) shell for extending nanoparticle circulation. The shell can be shed in response to the weakly acidic tumor microenvironment. The decrease in size and the increase in positive charge may cause the deep tumor penetration of drugs. We demonstrated that the bioactive nanovaccine dramatically enhance antigen presentation by dendritic cells (DCs) and drugs transportation into M1-like tumor-associated macrophages (TAMs) and tumor cells via size reduction and increasing positive charge caused by the weakly acidic TME. Such bioactive nanovaccine could remodel the immunosuppressive TME into an effector T cells favorable environment, leading to tumor growth inhibition in prophylactic and therapeutic E.G7-OVA tumor models. Furthermore, combining the bioactive nanovaccine with simultaneous anti-PD-1 antibody treatment leads to a long-term tumor inhibition, based on the optimal timing and sequence of PD-1 blockade against T cell receptor. This research provides a new strategy for the development of efficient cancer immunotherapy. KeAi Publishing 2022-03-11 /pmc/articles/PMC8958467/ /pubmed/35386322 http://dx.doi.org/10.1016/j.bioactmat.2022.03.008 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Xie, Xiaoxue
Feng, Yi
Zhang, Hanxi
Su, Qingqing
Song, Ting
Yang, Geng
Li, Ningxi
Wei, Xiaodan
Li, Tingting
Qin, Xiang
Li, Shun
Wu, Chunhui
Zhang, Xiaojuan
Wang, Guixue
Liu, Yiyao
Yang, Hong
Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy
title Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy
title_full Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy
title_fullStr Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy
title_full_unstemmed Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy
title_short Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy
title_sort remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8958467/
https://www.ncbi.nlm.nih.gov/pubmed/35386322
http://dx.doi.org/10.1016/j.bioactmat.2022.03.008
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