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Pore forming–mediated intracellular protein delivery for enhanced cancer immunotherapy
Directly delivering therapeutic proteins to their intracellular targets remains a great challenge. Here, we apply CD8(+) T cells to form pores on the tumor cells’ plasma membranes, enabling perfusion of ribonuclease A (RNase A) and granzyme B into cells, therefore effectively inducing tumor apoptosi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674288/ https://www.ncbi.nlm.nih.gov/pubmed/36399575 http://dx.doi.org/10.1126/sciadv.abq4659 |
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author | Zhou, Zhanwei Yang, Ruoxi Dong, Jingwen Di, Yongxiang Yang, Ying Huang, Ying Yang, Xue Liu, Wei Wang, Jinqiang Liu, Peifeng Gu, Zhen Sun, Minjie |
author_facet | Zhou, Zhanwei Yang, Ruoxi Dong, Jingwen Di, Yongxiang Yang, Ying Huang, Ying Yang, Xue Liu, Wei Wang, Jinqiang Liu, Peifeng Gu, Zhen Sun, Minjie |
author_sort | Zhou, Zhanwei |
collection | PubMed |
description | Directly delivering therapeutic proteins to their intracellular targets remains a great challenge. Here, we apply CD8(+) T cells to form pores on the tumor cells’ plasma membranes, enabling perfusion of ribonuclease A (RNase A) and granzyme B into cells, therefore effectively inducing tumor apoptosis and pyroptosis by activating caspase 3 and gasdermin E pathways to potentiate the CD8(+) T cell–mediated immunotherapy. Then, RNase A, programmed cell death ligand 1 antibody, and a photothermal agent were further loaded into an injectable hydrogel to treat the low immunogenic murine breast cancer. Notably, three courses of laser irradiation induced efficient cell apoptosis and immune activation, resulting in a notable therapeutic efficacy that 75% of the tumors were ablated without relapse. |
format | Online Article Text |
id | pubmed-9674288 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-96742882022-11-29 Pore forming–mediated intracellular protein delivery for enhanced cancer immunotherapy Zhou, Zhanwei Yang, Ruoxi Dong, Jingwen Di, Yongxiang Yang, Ying Huang, Ying Yang, Xue Liu, Wei Wang, Jinqiang Liu, Peifeng Gu, Zhen Sun, Minjie Sci Adv Biomedicine and Life Sciences Directly delivering therapeutic proteins to their intracellular targets remains a great challenge. Here, we apply CD8(+) T cells to form pores on the tumor cells’ plasma membranes, enabling perfusion of ribonuclease A (RNase A) and granzyme B into cells, therefore effectively inducing tumor apoptosis and pyroptosis by activating caspase 3 and gasdermin E pathways to potentiate the CD8(+) T cell–mediated immunotherapy. Then, RNase A, programmed cell death ligand 1 antibody, and a photothermal agent were further loaded into an injectable hydrogel to treat the low immunogenic murine breast cancer. Notably, three courses of laser irradiation induced efficient cell apoptosis and immune activation, resulting in a notable therapeutic efficacy that 75% of the tumors were ablated without relapse. American Association for the Advancement of Science 2022-11-18 /pmc/articles/PMC9674288/ /pubmed/36399575 http://dx.doi.org/10.1126/sciadv.abq4659 Text en Copyright © 2022 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). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://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 | Biomedicine and Life Sciences Zhou, Zhanwei Yang, Ruoxi Dong, Jingwen Di, Yongxiang Yang, Ying Huang, Ying Yang, Xue Liu, Wei Wang, Jinqiang Liu, Peifeng Gu, Zhen Sun, Minjie Pore forming–mediated intracellular protein delivery for enhanced cancer immunotherapy |
title | Pore forming–mediated intracellular protein delivery for enhanced cancer immunotherapy |
title_full | Pore forming–mediated intracellular protein delivery for enhanced cancer immunotherapy |
title_fullStr | Pore forming–mediated intracellular protein delivery for enhanced cancer immunotherapy |
title_full_unstemmed | Pore forming–mediated intracellular protein delivery for enhanced cancer immunotherapy |
title_short | Pore forming–mediated intracellular protein delivery for enhanced cancer immunotherapy |
title_sort | pore forming–mediated intracellular protein delivery for enhanced cancer immunotherapy |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674288/ https://www.ncbi.nlm.nih.gov/pubmed/36399575 http://dx.doi.org/10.1126/sciadv.abq4659 |
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