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Effect of tumour necrosis factor on the uptake of specific and control monoclonal antibodies in a human tumour xenograft model.
The investigations reported in this paper aim to exploit tumour necrosis factor (TNF)-induced vascular changes in an attempt to increase the tumour uptake of specific monoclonal antibody. The vascular permeability to monoclonal antibody of a human tumour xenograft increased 2.6-fold by 1 h post inje...
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
1995
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033735/ https://www.ncbi.nlm.nih.gov/pubmed/7710925 |
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author | Rowlinson-Busza, G. Maraveyas, A. Epenetos, A. A. |
author_facet | Rowlinson-Busza, G. Maraveyas, A. Epenetos, A. A. |
author_sort | Rowlinson-Busza, G. |
collection | PubMed |
description | The investigations reported in this paper aim to exploit tumour necrosis factor (TNF)-induced vascular changes in an attempt to increase the tumour uptake of specific monoclonal antibody. The vascular permeability to monoclonal antibody of a human tumour xenograft increased 2.6-fold by 1 h post injection of 2.5 x 10(3) U of TNF, although this effect was lost by 3 h. The normal tissues also demonstrated increased vascular permeability to IgG, but to a lesser extent. Liver permeability increased 1.5-fold at 1 h but returned to the control value by 6 h. Lung permeability increased 1.4-fold at 1 h post injection and returned to normal by 3 h. Muscle values were not significantly increased compared with controls. The blood activity was cleared more quickly in the TNF-treated mice (t1/2 beta = 101 h, compared with 121 h in control mice). This was probably due to the increased vascular permeability in normal organs of treated mice. At 1 day and 3 days post injection, the tumour uptake of the specific, but not the control, antibody was significantly increased by 25% and 29% respectively. This resulted in an increase in the area under the tumour activity curve, and therefore tumour radiation dose, of 25% in treated compared with control mice. In addition, a consequence of the faster blood clearance of the isotope in the TNF-treated mice was a reduction in the area under the blood activity curve of 12%, thereby reducing systemic toxicity. The increase in vascular permeability to IgG following TNF injection resulted in both specific and control antibodies having improved access to the tumour antigens, and a transient increase in uptake was observed. Only in the case of the specific antibody was the increase maintained, since this antibody binds to the available antigenic sites, whereas the control antibody was cleared from the tumour without binding. No evidence of tumour necrosis was observed at the TNF doses given, nor was there any toxicity to the mice. |
format | Text |
id | pubmed-2033735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1995 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-20337352009-09-10 Effect of tumour necrosis factor on the uptake of specific and control monoclonal antibodies in a human tumour xenograft model. Rowlinson-Busza, G. Maraveyas, A. Epenetos, A. A. Br J Cancer Research Article The investigations reported in this paper aim to exploit tumour necrosis factor (TNF)-induced vascular changes in an attempt to increase the tumour uptake of specific monoclonal antibody. The vascular permeability to monoclonal antibody of a human tumour xenograft increased 2.6-fold by 1 h post injection of 2.5 x 10(3) U of TNF, although this effect was lost by 3 h. The normal tissues also demonstrated increased vascular permeability to IgG, but to a lesser extent. Liver permeability increased 1.5-fold at 1 h but returned to the control value by 6 h. Lung permeability increased 1.4-fold at 1 h post injection and returned to normal by 3 h. Muscle values were not significantly increased compared with controls. The blood activity was cleared more quickly in the TNF-treated mice (t1/2 beta = 101 h, compared with 121 h in control mice). This was probably due to the increased vascular permeability in normal organs of treated mice. At 1 day and 3 days post injection, the tumour uptake of the specific, but not the control, antibody was significantly increased by 25% and 29% respectively. This resulted in an increase in the area under the tumour activity curve, and therefore tumour radiation dose, of 25% in treated compared with control mice. In addition, a consequence of the faster blood clearance of the isotope in the TNF-treated mice was a reduction in the area under the blood activity curve of 12%, thereby reducing systemic toxicity. The increase in vascular permeability to IgG following TNF injection resulted in both specific and control antibodies having improved access to the tumour antigens, and a transient increase in uptake was observed. Only in the case of the specific antibody was the increase maintained, since this antibody binds to the available antigenic sites, whereas the control antibody was cleared from the tumour without binding. No evidence of tumour necrosis was observed at the TNF doses given, nor was there any toxicity to the mice. Nature Publishing Group 1995-04 /pmc/articles/PMC2033735/ /pubmed/7710925 Text en 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 | Research Article Rowlinson-Busza, G. Maraveyas, A. Epenetos, A. A. Effect of tumour necrosis factor on the uptake of specific and control monoclonal antibodies in a human tumour xenograft model. |
title | Effect of tumour necrosis factor on the uptake of specific and control monoclonal antibodies in a human tumour xenograft model. |
title_full | Effect of tumour necrosis factor on the uptake of specific and control monoclonal antibodies in a human tumour xenograft model. |
title_fullStr | Effect of tumour necrosis factor on the uptake of specific and control monoclonal antibodies in a human tumour xenograft model. |
title_full_unstemmed | Effect of tumour necrosis factor on the uptake of specific and control monoclonal antibodies in a human tumour xenograft model. |
title_short | Effect of tumour necrosis factor on the uptake of specific and control monoclonal antibodies in a human tumour xenograft model. |
title_sort | effect of tumour necrosis factor on the uptake of specific and control monoclonal antibodies in a human tumour xenograft model. |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033735/ https://www.ncbi.nlm.nih.gov/pubmed/7710925 |
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