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Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy
Checkpoint blockade immunotherapy enhances systemic antitumor immune response by targeting T cell inhibitory pathways; however, inadequate T cell infiltration has limited its anticancer efficacy. Radiotherapy (RT) has local immunomodulatory effects that can alter the microenvironment of irradiated t...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003951/ https://www.ncbi.nlm.nih.gov/pubmed/29907739 http://dx.doi.org/10.1038/s41467-018-04703-w |
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author | Ni, Kaiyuan Lan, Guangxu Chan, Christina Quigley, Bryan Lu, Kuangda Aung, Theint Guo, Nining La Riviere, Patrick Weichselbaum, Ralph R. Lin, Wenbin |
author_facet | Ni, Kaiyuan Lan, Guangxu Chan, Christina Quigley, Bryan Lu, Kuangda Aung, Theint Guo, Nining La Riviere, Patrick Weichselbaum, Ralph R. Lin, Wenbin |
author_sort | Ni, Kaiyuan |
collection | PubMed |
description | Checkpoint blockade immunotherapy enhances systemic antitumor immune response by targeting T cell inhibitory pathways; however, inadequate T cell infiltration has limited its anticancer efficacy. Radiotherapy (RT) has local immunomodulatory effects that can alter the microenvironment of irradiated tumors to synergize with immune checkpoint blockade. However, even with high doses of radiation, RT has rarely elicited systemic immune responses. Herein, we report the design of two porous Hf-based nanoscale metal-organic frameworks (nMOFs) as highly effective radioenhancers that significantly outperform HfO(2), a clinically investigated radioenhancer in vitro and in vivo. Importantly, the combination of nMOF-mediated low-dose RT with an anti-programmed death-ligand 1 antibody effectively extends the local therapeutic effects of RT to distant tumors via abscopal effects. Our work establishes the feasibility of combining nMOF-mediated RT with immune checkpoint blockade to elicit systemic antitumor immunity in non-T cell-inflamed tumor phenotypes without normal tissue toxicity, promising to broaden the application of checkpoint blockade immunotherapy. |
format | Online Article Text |
id | pubmed-6003951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60039512018-06-18 Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy Ni, Kaiyuan Lan, Guangxu Chan, Christina Quigley, Bryan Lu, Kuangda Aung, Theint Guo, Nining La Riviere, Patrick Weichselbaum, Ralph R. Lin, Wenbin Nat Commun Article Checkpoint blockade immunotherapy enhances systemic antitumor immune response by targeting T cell inhibitory pathways; however, inadequate T cell infiltration has limited its anticancer efficacy. Radiotherapy (RT) has local immunomodulatory effects that can alter the microenvironment of irradiated tumors to synergize with immune checkpoint blockade. However, even with high doses of radiation, RT has rarely elicited systemic immune responses. Herein, we report the design of two porous Hf-based nanoscale metal-organic frameworks (nMOFs) as highly effective radioenhancers that significantly outperform HfO(2), a clinically investigated radioenhancer in vitro and in vivo. Importantly, the combination of nMOF-mediated low-dose RT with an anti-programmed death-ligand 1 antibody effectively extends the local therapeutic effects of RT to distant tumors via abscopal effects. Our work establishes the feasibility of combining nMOF-mediated RT with immune checkpoint blockade to elicit systemic antitumor immunity in non-T cell-inflamed tumor phenotypes without normal tissue toxicity, promising to broaden the application of checkpoint blockade immunotherapy. Nature Publishing Group UK 2018-06-15 /pmc/articles/PMC6003951/ /pubmed/29907739 http://dx.doi.org/10.1038/s41467-018-04703-w Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ni, Kaiyuan Lan, Guangxu Chan, Christina Quigley, Bryan Lu, Kuangda Aung, Theint Guo, Nining La Riviere, Patrick Weichselbaum, Ralph R. Lin, Wenbin Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy |
title | Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy |
title_full | Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy |
title_fullStr | Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy |
title_full_unstemmed | Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy |
title_short | Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy |
title_sort | nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003951/ https://www.ncbi.nlm.nih.gov/pubmed/29907739 http://dx.doi.org/10.1038/s41467-018-04703-w |
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