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A novel protein-drug conjugate, SSH20, demonstrates significant efficacy in caveolin-1-expressing tumors
In recent years, human serum albumin (HSA) has been characterized as an ideal drug carrier in the cancer arena. Caveolin-1 (Cav-1) has been established as the principal structural protein of caveolae and, thus, critical for caveolae-mediated endocytosis. Cav-1 has been shown to be overexpressed in c...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433067/ https://www.ncbi.nlm.nih.gov/pubmed/34553040 http://dx.doi.org/10.1016/j.omto.2021.07.013 |
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author | Robb, Ryan Kuo, Jimmy Chun-Tien Liu, Yang Corrales-Guerrero, Sergio Cui, Tiantian Hegazi, Ahmad Nagy, Gregory Lee, Robert J. Williams, Terence M. |
author_facet | Robb, Ryan Kuo, Jimmy Chun-Tien Liu, Yang Corrales-Guerrero, Sergio Cui, Tiantian Hegazi, Ahmad Nagy, Gregory Lee, Robert J. Williams, Terence M. |
author_sort | Robb, Ryan |
collection | PubMed |
description | In recent years, human serum albumin (HSA) has been characterized as an ideal drug carrier in the cancer arena. Caveolin-1 (Cav-1) has been established as the principal structural protein of caveolae and, thus, critical for caveolae-mediated endocytosis. Cav-1 has been shown to be overexpressed in cancers of the lung and pancreas, among others. We found that Cav-1 expression plays a critical role in both HSA uptake and response to albumin-based chemotherapies. As such, developing a novel albumin-based chemotherapy that is more selective for tumors with high Cav-1 expression or high levels of caveolar-endocytosis could have significant implications in biomarker-directed therapy. Herein, we present the development of a novel and effective HSA-SN-38 conjugate (SSH20). We find that SSH20 uptake decreases significantly by immunofluorescence assays and western blotting after silencing of Cav-1 expression through RNA interference. Decreased drug sensitivity occurs in Cav-1-depleted cells using cytotoxicity assays. Importantly, we find significantly reduced sensitivity to SSH20 in Cav-1-silenced tumors compared to Cav-1-expressing tumors in vivo. Notably, we show that SSH20 is significantly more potent than irinotecan in vitro and in vivo. Together, we have developed a novel HSA-conjugated chemotherapy that is potent, effective, safe, and demonstrates improved efficacy in high Cav-1-expressing tumors. |
format | Online Article Text |
id | pubmed-8433067 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-84330672021-09-21 A novel protein-drug conjugate, SSH20, demonstrates significant efficacy in caveolin-1-expressing tumors Robb, Ryan Kuo, Jimmy Chun-Tien Liu, Yang Corrales-Guerrero, Sergio Cui, Tiantian Hegazi, Ahmad Nagy, Gregory Lee, Robert J. Williams, Terence M. Mol Ther Oncolytics Original Article In recent years, human serum albumin (HSA) has been characterized as an ideal drug carrier in the cancer arena. Caveolin-1 (Cav-1) has been established as the principal structural protein of caveolae and, thus, critical for caveolae-mediated endocytosis. Cav-1 has been shown to be overexpressed in cancers of the lung and pancreas, among others. We found that Cav-1 expression plays a critical role in both HSA uptake and response to albumin-based chemotherapies. As such, developing a novel albumin-based chemotherapy that is more selective for tumors with high Cav-1 expression or high levels of caveolar-endocytosis could have significant implications in biomarker-directed therapy. Herein, we present the development of a novel and effective HSA-SN-38 conjugate (SSH20). We find that SSH20 uptake decreases significantly by immunofluorescence assays and western blotting after silencing of Cav-1 expression through RNA interference. Decreased drug sensitivity occurs in Cav-1-depleted cells using cytotoxicity assays. Importantly, we find significantly reduced sensitivity to SSH20 in Cav-1-silenced tumors compared to Cav-1-expressing tumors in vivo. Notably, we show that SSH20 is significantly more potent than irinotecan in vitro and in vivo. Together, we have developed a novel HSA-conjugated chemotherapy that is potent, effective, safe, and demonstrates improved efficacy in high Cav-1-expressing tumors. American Society of Gene & Cell Therapy 2021-08-06 /pmc/articles/PMC8433067/ /pubmed/34553040 http://dx.doi.org/10.1016/j.omto.2021.07.013 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Robb, Ryan Kuo, Jimmy Chun-Tien Liu, Yang Corrales-Guerrero, Sergio Cui, Tiantian Hegazi, Ahmad Nagy, Gregory Lee, Robert J. Williams, Terence M. A novel protein-drug conjugate, SSH20, demonstrates significant efficacy in caveolin-1-expressing tumors |
title | A novel protein-drug conjugate, SSH20, demonstrates significant efficacy in caveolin-1-expressing tumors |
title_full | A novel protein-drug conjugate, SSH20, demonstrates significant efficacy in caveolin-1-expressing tumors |
title_fullStr | A novel protein-drug conjugate, SSH20, demonstrates significant efficacy in caveolin-1-expressing tumors |
title_full_unstemmed | A novel protein-drug conjugate, SSH20, demonstrates significant efficacy in caveolin-1-expressing tumors |
title_short | A novel protein-drug conjugate, SSH20, demonstrates significant efficacy in caveolin-1-expressing tumors |
title_sort | novel protein-drug conjugate, ssh20, demonstrates significant efficacy in caveolin-1-expressing tumors |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433067/ https://www.ncbi.nlm.nih.gov/pubmed/34553040 http://dx.doi.org/10.1016/j.omto.2021.07.013 |
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