Therapeutic antitumor efficacy of tumor-derived autophagosome (DRibble) vaccine on head and neck cancer

Therapeutic antitumor efficacy of tumor-derived autophagosome (DRibble) vaccine on head and neck cancer

Hang Su,1,* Qiong Luo,2,* Hao Xie,3 Xiaofeng Huang,1 Yanhong Ni,1 Yongbin Mou,1 Qingang Hu1,4 1Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, 2State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 3Institute of Life...

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Main Authors: Su H, Luo Q, Xie H, Huang XF, Ni YH, Mou YB, Hu QG
Format: article
Language:EN
Published: Dove Medical Press 2015
Subjects:
Medicine (General)
R5-920
Online Access:https://doaj.org/article/0942a2efd90c4e3693fed021de97294f
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spelling oai:doaj.org-article:0942a2efd90c4e3693fed021de97294f2021-12-02T04:23:13ZTherapeutic antitumor efficacy of tumor-derived autophagosome (DRibble) vaccine on head and neck cancer1178-2013https://doaj.org/article/0942a2efd90c4e3693fed021de97294f2015-03-01T00:00:00Zhttp://www.dovepress.com/therapeutic-antitumor-efficacy-of-tumor-derived-autophagosome-dribble--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Hang Su,1,* Qiong Luo,2,* Hao Xie,3 Xiaofeng Huang,1 Yanhong Ni,1 Yongbin Mou,1 Qingang Hu1,4 1Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, 2State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 3Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, People’s Republic of China; 4Leeds Dental Institute, Faculty of Medicine and Health, University of Leeds, Leeds, UK *These authors contributed equally to this work Purpose: Vaccines play important roles in antitumor biotherapy. Autophagy in tumor cells plays a critical role in depredating proteins, including tumor-specific antigens and tumor-associated antigens. We aimed to induce and collect tumor-derived autophagosomes (DRibbles) from tumor cells as a novel antitumor vaccine by inhibiting the functions of proteasomes and lysosomes.Materials and methods: DRibbles were prepared and their morphological and autophagic properties characterized. Dendritic cells (DCs) generated from the bone marrow monocytes of mice were cocultured with DRibbles, then surface molecules of DCs and B cells, as well as apoptosis of DCs, were determined by flow cytometry. Meanwhile, functional properties of the DRibble-DCs were examined by mixed lymphocyte reactions and animal experiments.Results: The diameter of autophagic nanoparticles with spherical and double-membrane structure was between 200 nm and 500 nm. DRibbles resulted in the upregulation of costimulatory molecules CD40 and CD86 as well as major histocompatibility complex (MHC)-I molecules on DCs, but not MHC-II. The expressions of CD40, CD80, and CD86 and that of MHC-II molecules on B cells were also upregulated. Moreover, suppression of tumor growth and lifetime prolongation was observed in DRibble-DC-vaccinated tumor-bearing mice.Conclusion: Our results demonstrate that naïve T cells can be activated effectively by DC cross-presenting antigens on upregulated MHC-I, suggesting that DRibbles be deployed as an effective antitumor vaccine for head and neck cancer immunotherapy in clinical trials. Keywords: autophagy, nanoparticles, dendritic cells, antitumor immunity, head and neck cancerSu HLuo QXie HHuang XFNi YHMou YBHu QGDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 1921-1930 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Su H
Luo Q
Xie H
Huang XF
Ni YH
Mou YB
Hu QG
Therapeutic antitumor efficacy of tumor-derived autophagosome (DRibble) vaccine on head and neck cancer
description Hang Su,1,* Qiong Luo,2,* Hao Xie,3 Xiaofeng Huang,1 Yanhong Ni,1 Yongbin Mou,1 Qingang Hu1,4 1Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, 2State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 3Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, People’s Republic of China; 4Leeds Dental Institute, Faculty of Medicine and Health, University of Leeds, Leeds, UK *These authors contributed equally to this work Purpose: Vaccines play important roles in antitumor biotherapy. Autophagy in tumor cells plays a critical role in depredating proteins, including tumor-specific antigens and tumor-associated antigens. We aimed to induce and collect tumor-derived autophagosomes (DRibbles) from tumor cells as a novel antitumor vaccine by inhibiting the functions of proteasomes and lysosomes.Materials and methods: DRibbles were prepared and their morphological and autophagic properties characterized. Dendritic cells (DCs) generated from the bone marrow monocytes of mice were cocultured with DRibbles, then surface molecules of DCs and B cells, as well as apoptosis of DCs, were determined by flow cytometry. Meanwhile, functional properties of the DRibble-DCs were examined by mixed lymphocyte reactions and animal experiments.Results: The diameter of autophagic nanoparticles with spherical and double-membrane structure was between 200 nm and 500 nm. DRibbles resulted in the upregulation of costimulatory molecules CD40 and CD86 as well as major histocompatibility complex (MHC)-I molecules on DCs, but not MHC-II. The expressions of CD40, CD80, and CD86 and that of MHC-II molecules on B cells were also upregulated. Moreover, suppression of tumor growth and lifetime prolongation was observed in DRibble-DC-vaccinated tumor-bearing mice.Conclusion: Our results demonstrate that naïve T cells can be activated effectively by DC cross-presenting antigens on upregulated MHC-I, suggesting that DRibbles be deployed as an effective antitumor vaccine for head and neck cancer immunotherapy in clinical trials. Keywords: autophagy, nanoparticles, dendritic cells, antitumor immunity, head and neck cancer
format article
author Su H
Luo Q
Xie H
Huang XF
Ni YH
Mou YB
Hu QG
author_facet Su H
Luo Q
Xie H
Huang XF
Ni YH
Mou YB
Hu QG
author_sort Su H
title Therapeutic antitumor efficacy of tumor-derived autophagosome (DRibble) vaccine on head and neck cancer
title_short Therapeutic antitumor efficacy of tumor-derived autophagosome (DRibble) vaccine on head and neck cancer
title_full Therapeutic antitumor efficacy of tumor-derived autophagosome (DRibble) vaccine on head and neck cancer
title_fullStr Therapeutic antitumor efficacy of tumor-derived autophagosome (DRibble) vaccine on head and neck cancer
title_full_unstemmed Therapeutic antitumor efficacy of tumor-derived autophagosome (DRibble) vaccine on head and neck cancer
title_sort therapeutic antitumor efficacy of tumor-derived autophagosome (dribble) vaccine on head and neck cancer
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/0942a2efd90c4e3693fed021de97294f
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AT luoq therapeuticantitumorefficacyoftumorderivedautophagosomedribblevaccineonheadandnbspneckcancer
AT xieh therapeuticantitumorefficacyoftumorderivedautophagosomedribblevaccineonheadandnbspneckcancer
AT huangxf therapeuticantitumorefficacyoftumorderivedautophagosomedribblevaccineonheadandnbspneckcancer
AT niyh therapeuticantitumorefficacyoftumorderivedautophagosomedribblevaccineonheadandnbspneckcancer
AT mouyb therapeuticantitumorefficacyoftumorderivedautophagosomedribblevaccineonheadandnbspneckcancer
AT huqg therapeuticantitumorefficacyoftumorderivedautophagosomedribblevaccineonheadandnbspneckcancer
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