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Selective cytotoxicity against human tumour cells by a vindesine-monoclonal antibody conjugate.

The anti-mitotic drug vindesine was coupled chemically to a monoclonal antibody raised originally against the human osteogenic sarcoma cell line, 791T. The cytotoxicity of the conjugate in vitro was tested, in comparison with free vindesine, against sarcoma 791T and other antigenically cross-reactiv...

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Autores principales: Embleton, M. J., Rowland, G. F., Simmonds, R. G., Jacobs, E., Marsden, C. H., Baldwin, R. W.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1983
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2011258/
https://www.ncbi.nlm.nih.gov/pubmed/6571783
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author Embleton, M. J.
Rowland, G. F.
Simmonds, R. G.
Jacobs, E.
Marsden, C. H.
Baldwin, R. W.
author_facet Embleton, M. J.
Rowland, G. F.
Simmonds, R. G.
Jacobs, E.
Marsden, C. H.
Baldwin, R. W.
author_sort Embleton, M. J.
collection PubMed
description The anti-mitotic drug vindesine was coupled chemically to a monoclonal antibody raised originally against the human osteogenic sarcoma cell line, 791T. The cytotoxicity of the conjugate in vitro was tested, in comparison with free vindesine, against sarcoma 791T and other antigenically cross-reactive osteogenic sarcoma-cell lines, and also against tumour cell lines which have no detectable reaction with the monoclonal antibody. Continuous exposure of cultured 791T cells indicated that the vindesine was partially inactivated following conjugation since the conjugate was less toxic than the free drug. However, antibody-binding activity was essentially preserved following conjugation. Despite diminished drug activity in the conjugate, assays designed to mimic antibody binding to tumour in which target cells were treated with conjugate and washed before culture, showed selective cytotoxicity for osteogenic sarcoma lines with little or no effect on non-cross reactive control cells. In comparison, free vindesine was toxic equally for all cell lines and free antibody was non-toxic. These studies indicate that conjugation of a cytotoxic agent to a monoclonal antibody can confer on that agent selectivity for a particular target cell type which is recognised by the antibody.
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spelling pubmed-20112582009-09-10 Selective cytotoxicity against human tumour cells by a vindesine-monoclonal antibody conjugate. Embleton, M. J. Rowland, G. F. Simmonds, R. G. Jacobs, E. Marsden, C. H. Baldwin, R. W. Br J Cancer Research Article The anti-mitotic drug vindesine was coupled chemically to a monoclonal antibody raised originally against the human osteogenic sarcoma cell line, 791T. The cytotoxicity of the conjugate in vitro was tested, in comparison with free vindesine, against sarcoma 791T and other antigenically cross-reactive osteogenic sarcoma-cell lines, and also against tumour cell lines which have no detectable reaction with the monoclonal antibody. Continuous exposure of cultured 791T cells indicated that the vindesine was partially inactivated following conjugation since the conjugate was less toxic than the free drug. However, antibody-binding activity was essentially preserved following conjugation. Despite diminished drug activity in the conjugate, assays designed to mimic antibody binding to tumour in which target cells were treated with conjugate and washed before culture, showed selective cytotoxicity for osteogenic sarcoma lines with little or no effect on non-cross reactive control cells. In comparison, free vindesine was toxic equally for all cell lines and free antibody was non-toxic. These studies indicate that conjugation of a cytotoxic agent to a monoclonal antibody can confer on that agent selectivity for a particular target cell type which is recognised by the antibody. Nature Publishing Group 1983-01 /pmc/articles/PMC2011258/ /pubmed/6571783 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
Embleton, M. J.
Rowland, G. F.
Simmonds, R. G.
Jacobs, E.
Marsden, C. H.
Baldwin, R. W.
Selective cytotoxicity against human tumour cells by a vindesine-monoclonal antibody conjugate.
title Selective cytotoxicity against human tumour cells by a vindesine-monoclonal antibody conjugate.
title_full Selective cytotoxicity against human tumour cells by a vindesine-monoclonal antibody conjugate.
title_fullStr Selective cytotoxicity against human tumour cells by a vindesine-monoclonal antibody conjugate.
title_full_unstemmed Selective cytotoxicity against human tumour cells by a vindesine-monoclonal antibody conjugate.
title_short Selective cytotoxicity against human tumour cells by a vindesine-monoclonal antibody conjugate.
title_sort selective cytotoxicity against human tumour cells by a vindesine-monoclonal antibody conjugate.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2011258/
https://www.ncbi.nlm.nih.gov/pubmed/6571783
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