Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy

Autologous tumor cells and cell-derived secretions (CDS) can induce antitumor immune responses. The conditions in which cells are cultured and treated impact CDS, and cellular insults alter their composition and function. In this study, we generated CDS from tumor cells exposed to normal culture con...

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Autores principales: Yuhan Zhou, Ting Ye, Chengzhi Ye, Chao Wan, Siyue Yuan, Yushuai Liu, Tianyu Li, Fagang Jiang, Jonathan F. Lovell, Honglin Jin, Jing Chen
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Lenguaje:EN
Publicado: KeAi Communications Co., Ltd. 2022
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Acceso en línea:https://doaj.org/article/e2b468649da94e4c8b60ddbf32767fd5
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spelling oai:doaj.org-article:e2b468649da94e4c8b60ddbf32767fd52021-11-10T04:30:43ZSecretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy2452-199X10.1016/j.bioactmat.2021.07.019https://doaj.org/article/e2b468649da94e4c8b60ddbf32767fd52022-03-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2452199X21003510https://doaj.org/toc/2452-199XAutologous tumor cells and cell-derived secretions (CDS) can induce antitumor immune responses. The conditions in which cells are cultured and treated impact CDS, and cellular insults alter their composition and function. In this study, we generated CDS from tumor cells exposed to normal culture conditions, hypoxia, cisplatin, radiotherapy, photodynamic therapy, or hypochlorous acid (HOCl). In vitro HOCl-CDS showed the strongest stimulatory effects on dendritic cells and macrophages compared to CDS generated by hypoxia, cisplatin, radiotherapy or photodynamic therapy. To improve HOCl-CDS activity at the tumor site, we loaded HOCl-CDS into a melittin-encapsulated hydrogel scaffold. When injected intratumorally, the HOCl-CDS hydrogel promoted tumor cell death, cytotoxic T lymphocyte infiltration, and tumor-associated macrophage reprogramming towards an M1 phenotype. The hydrogel inhibited tumor growth and prolonged the survival of mice bearing B16–F10 melanoma. Furthermore, hydrogel-delivered HOCl-CDS augmented the antitumor effects of immune checkpoint blockade. These results underscore the importance of the CDS generation method and delivery approach for improving cancer immunotherapy.Yuhan ZhouTing YeChengzhi YeChao WanSiyue YuanYushuai LiuTianyu LiFagang JiangJonathan F. LovellHonglin JinJing ChenKeAi Communications Co., Ltd.articleCancer immunotherapyHydrogelMelittinAnti-PD-1Cell-derived secretionsMaterials of engineering and construction. Mechanics of materialsTA401-492Biology (General)QH301-705.5ENBioactive Materials, Vol 9, Iss , Pp 541-553 (2022)
institution DOAJ
collection DOAJ
language EN
topic Cancer immunotherapy
Hydrogel
Melittin
Anti-PD-1
Cell-derived secretions
Materials of engineering and construction. Mechanics of materials
TA401-492
Biology (General)
QH301-705.5
spellingShingle Cancer immunotherapy
Hydrogel
Melittin
Anti-PD-1
Cell-derived secretions
Materials of engineering and construction. Mechanics of materials
TA401-492
Biology (General)
QH301-705.5
Yuhan Zhou
Ting Ye
Chengzhi Ye
Chao Wan
Siyue Yuan
Yushuai Liu
Tianyu Li
Fagang Jiang
Jonathan F. Lovell
Honglin Jin
Jing Chen
Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy
description Autologous tumor cells and cell-derived secretions (CDS) can induce antitumor immune responses. The conditions in which cells are cultured and treated impact CDS, and cellular insults alter their composition and function. In this study, we generated CDS from tumor cells exposed to normal culture conditions, hypoxia, cisplatin, radiotherapy, photodynamic therapy, or hypochlorous acid (HOCl). In vitro HOCl-CDS showed the strongest stimulatory effects on dendritic cells and macrophages compared to CDS generated by hypoxia, cisplatin, radiotherapy or photodynamic therapy. To improve HOCl-CDS activity at the tumor site, we loaded HOCl-CDS into a melittin-encapsulated hydrogel scaffold. When injected intratumorally, the HOCl-CDS hydrogel promoted tumor cell death, cytotoxic T lymphocyte infiltration, and tumor-associated macrophage reprogramming towards an M1 phenotype. The hydrogel inhibited tumor growth and prolonged the survival of mice bearing B16–F10 melanoma. Furthermore, hydrogel-delivered HOCl-CDS augmented the antitumor effects of immune checkpoint blockade. These results underscore the importance of the CDS generation method and delivery approach for improving cancer immunotherapy.
format article
author Yuhan Zhou
Ting Ye
Chengzhi Ye
Chao Wan
Siyue Yuan
Yushuai Liu
Tianyu Li
Fagang Jiang
Jonathan F. Lovell
Honglin Jin
Jing Chen
author_facet Yuhan Zhou
Ting Ye
Chengzhi Ye
Chao Wan
Siyue Yuan
Yushuai Liu
Tianyu Li
Fagang Jiang
Jonathan F. Lovell
Honglin Jin
Jing Chen
author_sort Yuhan Zhou
title Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy
title_short Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy
title_full Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy
title_fullStr Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy
title_full_unstemmed Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy
title_sort secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy
publisher KeAi Communications Co., Ltd.
publishDate 2022
url https://doaj.org/article/e2b468649da94e4c8b60ddbf32767fd5
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