Ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy

Abstract Lack of pre-existing tumor infiltrated T cells resulting in resistance to programmed cell death protein 1 (PD-1) blockade therapies can be solved by combining with anti-cancer vaccines and CpG-ODN in increasing T cell expansion and infiltration. Therefore, we prepared an ex vivo dendritic c...

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Autores principales: Mona Yazdani, Zahra Gholizadeh, Amin Reza Nikpoor, Nema Mohamadian Roshan, Mahmoud Reza Jaafari, Ali Badiee
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/2af50bb7f73544da8892e80e7cefb5f6
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spelling oai:doaj.org-article:2af50bb7f73544da8892e80e7cefb5f62021-12-02T17:55:04ZEx vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy10.1038/s41598-021-94250-02045-2322https://doaj.org/article/2af50bb7f73544da8892e80e7cefb5f62021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94250-0https://doaj.org/toc/2045-2322Abstract Lack of pre-existing tumor infiltrated T cells resulting in resistance to programmed cell death protein 1 (PD-1) blockade therapies can be solved by combining with anti-cancer vaccines and CpG-ODN in increasing T cell expansion and infiltration. Therefore, we prepared an ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of either liposomal or non-liposomal gp100 antigen (2.8 µg) plus CpG-ODN (800 ng) formulations and evaluated its anti-tumor activity in combination with anti-PD-1 therapy. Our results showed a combination of liposomal peptide plus CpG-ODN pulsed DC with anti-PD-1 antibody was more efficacious, as evidenced by a significant increase in Teff/Treg TILs with a marked fourfold elevation of IFN-γ expression level in the tumor site of treated mice which reversed resistance to PD-1 blockade in a CD8 T cell-dependent manner. Furthermore, this combination also led to a remarkable tumor remission and prolonged survival rate in melanoma-bearing mice compared to non-liposomal peptide plus CpG-ODN or single-treated liposomal peptide formulations. Our results provide essential insights to devise combining regimens to improve the efficacy of immune checkpoint blockers even by a low dose of peptide and CpG-ODN.Mona YazdaniZahra GholizadehAmin Reza NikpoorNema Mohamadian RoshanMahmoud Reza JaafariAli BadieeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Mona Yazdani
Zahra Gholizadeh
Amin Reza Nikpoor
Nema Mohamadian Roshan
Mahmoud Reza Jaafari
Ali Badiee
Ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy
description Abstract Lack of pre-existing tumor infiltrated T cells resulting in resistance to programmed cell death protein 1 (PD-1) blockade therapies can be solved by combining with anti-cancer vaccines and CpG-ODN in increasing T cell expansion and infiltration. Therefore, we prepared an ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of either liposomal or non-liposomal gp100 antigen (2.8 µg) plus CpG-ODN (800 ng) formulations and evaluated its anti-tumor activity in combination with anti-PD-1 therapy. Our results showed a combination of liposomal peptide plus CpG-ODN pulsed DC with anti-PD-1 antibody was more efficacious, as evidenced by a significant increase in Teff/Treg TILs with a marked fourfold elevation of IFN-γ expression level in the tumor site of treated mice which reversed resistance to PD-1 blockade in a CD8 T cell-dependent manner. Furthermore, this combination also led to a remarkable tumor remission and prolonged survival rate in melanoma-bearing mice compared to non-liposomal peptide plus CpG-ODN or single-treated liposomal peptide formulations. Our results provide essential insights to devise combining regimens to improve the efficacy of immune checkpoint blockers even by a low dose of peptide and CpG-ODN.
format article
author Mona Yazdani
Zahra Gholizadeh
Amin Reza Nikpoor
Nema Mohamadian Roshan
Mahmoud Reza Jaafari
Ali Badiee
author_facet Mona Yazdani
Zahra Gholizadeh
Amin Reza Nikpoor
Nema Mohamadian Roshan
Mahmoud Reza Jaafari
Ali Badiee
author_sort Mona Yazdani
title Ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy
title_short Ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy
title_full Ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy
title_fullStr Ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy
title_full_unstemmed Ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy
title_sort ex vivo dendritic cell-based (dc) vaccine pulsed with a low dose of liposomal antigen and cpg-odn improved pd-1 blockade immunotherapy
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/2af50bb7f73544da8892e80e7cefb5f6
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