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Efficacy of immunoliposomes on cancer models in a cell-surface-antigen-density-dependent manner
We have recently established a cancer-reactive human monoclonal antibody, GAH, with a positive ratio of over 90% against stomach cancer. GAH was formulated as polyethyleneglycol (PEG)-modified immunoliposomal doxorubicin (DXR) (ILD) and its efficacy was examined against gastrointestinal human cancer...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394358/ https://www.ncbi.nlm.nih.gov/pubmed/14562030 http://dx.doi.org/10.1038/sj.bjc.6601341 |
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author | Hosokawa, S Tagawa, T Niki, H Hirakawa, Y Nohga, K Nagaike, K |
author_facet | Hosokawa, S Tagawa, T Niki, H Hirakawa, Y Nohga, K Nagaike, K |
author_sort | Hosokawa, S |
collection | PubMed |
description | We have recently established a cancer-reactive human monoclonal antibody, GAH, with a positive ratio of over 90% against stomach cancer. GAH was formulated as polyethyleneglycol (PEG)-modified immunoliposomal doxorubicin (DXR) (ILD) and its efficacy was examined against gastrointestinal human cancers. In in vitro studies, a comparison of ILD with PEG-modified liposomal DXR (LD) demonstrated that ILD had dose-dependent cytotoxicity for GAH-reactive B37 cancer cells, but not LD. In concordance with this result, microscopic observations showed that ILD was bound to and GAH-dependently internalised by B37 cells. In in vivo studies, ILD exhibited significantly greater antitumour activity on cancer xenograft models than LD or free DXR. The relation between efficacy and antigen density was examined on 10 xenograft models bearing cancer cells with varying GAH reactivity. Immunoliposomal doxorubicin therapeutic activity correlated with the antigen density, with a minimum number being required. Also, ILD revealed strong antitumour activity on cancers with low sensitivity to DXR or LD, suggesting that ILD overcame the DXR resistance of antigen-positive cancer cells. Thus, these results show that GAH endows liposomes with targeting activity, resulting in strong efficacy against gastrointestinal cancers. |
format | Text |
id | pubmed-2394358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23943582009-09-10 Efficacy of immunoliposomes on cancer models in a cell-surface-antigen-density-dependent manner Hosokawa, S Tagawa, T Niki, H Hirakawa, Y Nohga, K Nagaike, K Br J Cancer Experimental Therapeutics We have recently established a cancer-reactive human monoclonal antibody, GAH, with a positive ratio of over 90% against stomach cancer. GAH was formulated as polyethyleneglycol (PEG)-modified immunoliposomal doxorubicin (DXR) (ILD) and its efficacy was examined against gastrointestinal human cancers. In in vitro studies, a comparison of ILD with PEG-modified liposomal DXR (LD) demonstrated that ILD had dose-dependent cytotoxicity for GAH-reactive B37 cancer cells, but not LD. In concordance with this result, microscopic observations showed that ILD was bound to and GAH-dependently internalised by B37 cells. In in vivo studies, ILD exhibited significantly greater antitumour activity on cancer xenograft models than LD or free DXR. The relation between efficacy and antigen density was examined on 10 xenograft models bearing cancer cells with varying GAH reactivity. Immunoliposomal doxorubicin therapeutic activity correlated with the antigen density, with a minimum number being required. Also, ILD revealed strong antitumour activity on cancers with low sensitivity to DXR or LD, suggesting that ILD overcame the DXR resistance of antigen-positive cancer cells. Thus, these results show that GAH endows liposomes with targeting activity, resulting in strong efficacy against gastrointestinal cancers. Nature Publishing Group 2003-10-20 2003-10-14 /pmc/articles/PMC2394358/ /pubmed/14562030 http://dx.doi.org/10.1038/sj.bjc.6601341 Text en Copyright © 2003 Cancer Research UK https://creativecommons.org/licenses/by/4.0/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 https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Experimental Therapeutics Hosokawa, S Tagawa, T Niki, H Hirakawa, Y Nohga, K Nagaike, K Efficacy of immunoliposomes on cancer models in a cell-surface-antigen-density-dependent manner |
title | Efficacy of immunoliposomes on cancer models in a cell-surface-antigen-density-dependent manner |
title_full | Efficacy of immunoliposomes on cancer models in a cell-surface-antigen-density-dependent manner |
title_fullStr | Efficacy of immunoliposomes on cancer models in a cell-surface-antigen-density-dependent manner |
title_full_unstemmed | Efficacy of immunoliposomes on cancer models in a cell-surface-antigen-density-dependent manner |
title_short | Efficacy of immunoliposomes on cancer models in a cell-surface-antigen-density-dependent manner |
title_sort | efficacy of immunoliposomes on cancer models in a cell-surface-antigen-density-dependent manner |
topic | Experimental Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394358/ https://www.ncbi.nlm.nih.gov/pubmed/14562030 http://dx.doi.org/10.1038/sj.bjc.6601341 |
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