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Elimination of established tumors with nanodisc-based combination chemoimmunotherapy
Although immune checkpoint blockade has shown initial success for various cancers, only a small subset of patients benefits from this therapy. Some chemotherapeutic drugs have been reported to induce antitumor T cell responses, prompting a number of clinical trials on combination chemoimmunotherapy....
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906077/ https://www.ncbi.nlm.nih.gov/pubmed/29675465 http://dx.doi.org/10.1126/sciadv.aao1736 |
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author | Kuai, Rui Yuan, Wenmin Son, Sejin Nam, Jutaek Xu, Yao Fan, Yuchen Schwendeman, Anna Moon, James J. |
author_facet | Kuai, Rui Yuan, Wenmin Son, Sejin Nam, Jutaek Xu, Yao Fan, Yuchen Schwendeman, Anna Moon, James J. |
author_sort | Kuai, Rui |
collection | PubMed |
description | Although immune checkpoint blockade has shown initial success for various cancers, only a small subset of patients benefits from this therapy. Some chemotherapeutic drugs have been reported to induce antitumor T cell responses, prompting a number of clinical trials on combination chemoimmunotherapy. However, how to achieve potent immune activation with traditional chemotherapeutics in a manner that is safe, effective, and compatible with immunotherapy remains unclear. We show that high-density lipoprotein–mimicking nanodiscs loaded with doxorubicin (DOX), a widely used chemotherapeutic agent, can potentiate immune checkpoint blockade in murine tumor models. Delivery of DOX via nanodiscs triggered immunogenic cell death of cancer cells and exerted antitumor efficacy without any overt off-target side effects. “Priming” tumors with DOX-carrying nanodiscs elicited robust antitumor CD8(+) T cell responses while broadening their epitope recognition to tumor-associated antigens, neoantigens, and intact whole tumor cells. Combination chemoimmunotherapy with nanodiscs plus anti–programmed death 1 therapy induced complete regression of established CT26 and MC38 colon carcinoma tumors in 80 to 88% of animals and protected survivors against tumor recurrence. Our work provides a new, generalizable framework for using nanoparticle-based chemotherapy to initiate antitumor immunity and sensitize tumors to immune checkpoint blockade. |
format | Online Article Text |
id | pubmed-5906077 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-59060772018-04-19 Elimination of established tumors with nanodisc-based combination chemoimmunotherapy Kuai, Rui Yuan, Wenmin Son, Sejin Nam, Jutaek Xu, Yao Fan, Yuchen Schwendeman, Anna Moon, James J. Sci Adv Research Articles Although immune checkpoint blockade has shown initial success for various cancers, only a small subset of patients benefits from this therapy. Some chemotherapeutic drugs have been reported to induce antitumor T cell responses, prompting a number of clinical trials on combination chemoimmunotherapy. However, how to achieve potent immune activation with traditional chemotherapeutics in a manner that is safe, effective, and compatible with immunotherapy remains unclear. We show that high-density lipoprotein–mimicking nanodiscs loaded with doxorubicin (DOX), a widely used chemotherapeutic agent, can potentiate immune checkpoint blockade in murine tumor models. Delivery of DOX via nanodiscs triggered immunogenic cell death of cancer cells and exerted antitumor efficacy without any overt off-target side effects. “Priming” tumors with DOX-carrying nanodiscs elicited robust antitumor CD8(+) T cell responses while broadening their epitope recognition to tumor-associated antigens, neoantigens, and intact whole tumor cells. Combination chemoimmunotherapy with nanodiscs plus anti–programmed death 1 therapy induced complete regression of established CT26 and MC38 colon carcinoma tumors in 80 to 88% of animals and protected survivors against tumor recurrence. Our work provides a new, generalizable framework for using nanoparticle-based chemotherapy to initiate antitumor immunity and sensitize tumors to immune checkpoint blockade. American Association for the Advancement of Science 2018-04-18 /pmc/articles/PMC5906077/ /pubmed/29675465 http://dx.doi.org/10.1126/sciadv.aao1736 Text en Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Kuai, Rui Yuan, Wenmin Son, Sejin Nam, Jutaek Xu, Yao Fan, Yuchen Schwendeman, Anna Moon, James J. Elimination of established tumors with nanodisc-based combination chemoimmunotherapy |
title | Elimination of established tumors with nanodisc-based combination chemoimmunotherapy |
title_full | Elimination of established tumors with nanodisc-based combination chemoimmunotherapy |
title_fullStr | Elimination of established tumors with nanodisc-based combination chemoimmunotherapy |
title_full_unstemmed | Elimination of established tumors with nanodisc-based combination chemoimmunotherapy |
title_short | Elimination of established tumors with nanodisc-based combination chemoimmunotherapy |
title_sort | elimination of established tumors with nanodisc-based combination chemoimmunotherapy |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906077/ https://www.ncbi.nlm.nih.gov/pubmed/29675465 http://dx.doi.org/10.1126/sciadv.aao1736 |
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