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Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positive B-cells

This paper describes a bi-specific antibody, which was called BIS20x3. It retargets CD3ɛ-positive cells (T-cells) to CD20-positive cells and was obtained by hybrid–hybridoma fusion. BIS20x3 could be isolated readily from quadroma culture supernatant and retained all the signalling characteristics as...

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Autores principales: Withoff, S, Bijman, M N A, Stel, A J, Delahaye, L, Calogero, A, Jonge, M W A de, Kroesen, B J, Leij, L de
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363855/
https://www.ncbi.nlm.nih.gov/pubmed/11308263
http://dx.doi.org/10.1054/bjoc.2000.1707
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author Withoff, S
Bijman, M N A
Stel, A J
Delahaye, L
Calogero, A
Jonge, M W A de
Kroesen, B J
Leij, L de
author_facet Withoff, S
Bijman, M N A
Stel, A J
Delahaye, L
Calogero, A
Jonge, M W A de
Kroesen, B J
Leij, L de
author_sort Withoff, S
collection PubMed
description This paper describes a bi-specific antibody, which was called BIS20x3. It retargets CD3ɛ-positive cells (T-cells) to CD20-positive cells and was obtained by hybrid–hybridoma fusion. BIS20x3 could be isolated readily from quadroma culture supernatant and retained all the signalling characteristics associated with both of its chains. Cross-linking of BIS20x3 on Ramos cells leads to DNA fragmentation percentages similar to those obtained after Rituximab-cross-linking. Cross-linking of BIS20x3 on T-cells using cross-linking F(ab′)2-fragments induced T-cell activation. Indirect cross-linking of T-cell-bound BIS20x3 via Ramos cells hyper-activated the T-cells. Furthermore, it was demonstrated that BIS20x3 effectively re-targets T-cells to B-cells, leading to high B-cell cytotoxicity. The results presented in this paper show that BIS20x3 is fully functional in retargeting T-cells to B-cells and suggest that B-cell lymphomas may represent ideal targets for T-cell retargeting bi-specific antibodies, because the retargeted T-cell is maximally stimulated in the presence of B-cells. Additionally, since B-cells may up-regulate CD95/ Fas expression upon binding of CD20-directed antibodies, B-cells will become even more sensitive for T-cell mediated killing via CD95L/ Fas L, and therefore supports the intention to use T-cell retargeting bi-specific antibodies recognizing CD20 on B-cell malignancies as a treatment modality for these diseases. © 2001 Cancer Research Campaign http://www.bjcancer.com
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spelling pubmed-23638552009-09-10 Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positive B-cells Withoff, S Bijman, M N A Stel, A J Delahaye, L Calogero, A Jonge, M W A de Kroesen, B J Leij, L de Br J Cancer Regular Article This paper describes a bi-specific antibody, which was called BIS20x3. It retargets CD3ɛ-positive cells (T-cells) to CD20-positive cells and was obtained by hybrid–hybridoma fusion. BIS20x3 could be isolated readily from quadroma culture supernatant and retained all the signalling characteristics associated with both of its chains. Cross-linking of BIS20x3 on Ramos cells leads to DNA fragmentation percentages similar to those obtained after Rituximab-cross-linking. Cross-linking of BIS20x3 on T-cells using cross-linking F(ab′)2-fragments induced T-cell activation. Indirect cross-linking of T-cell-bound BIS20x3 via Ramos cells hyper-activated the T-cells. Furthermore, it was demonstrated that BIS20x3 effectively re-targets T-cells to B-cells, leading to high B-cell cytotoxicity. The results presented in this paper show that BIS20x3 is fully functional in retargeting T-cells to B-cells and suggest that B-cell lymphomas may represent ideal targets for T-cell retargeting bi-specific antibodies, because the retargeted T-cell is maximally stimulated in the presence of B-cells. Additionally, since B-cells may up-regulate CD95/ Fas expression upon binding of CD20-directed antibodies, B-cells will become even more sensitive for T-cell mediated killing via CD95L/ Fas L, and therefore supports the intention to use T-cell retargeting bi-specific antibodies recognizing CD20 on B-cell malignancies as a treatment modality for these diseases. © 2001 Cancer Research Campaign http://www.bjcancer.com Nature Publishing Group 2001-04 /pmc/articles/PMC2363855/ /pubmed/11308263 http://dx.doi.org/10.1054/bjoc.2000.1707 Text en Copyright © 2001 Cancer Research Campaign 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 Regular Article
Withoff, S
Bijman, M N A
Stel, A J
Delahaye, L
Calogero, A
Jonge, M W A de
Kroesen, B J
Leij, L de
Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positive B-cells
title Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positive B-cells
title_full Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positive B-cells
title_fullStr Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positive B-cells
title_full_unstemmed Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positive B-cells
title_short Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positive B-cells
title_sort characterization of bis20x3, a bi-specific antibody activating and retargeting t-cells to cd20-positive b-cells
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363855/
https://www.ncbi.nlm.nih.gov/pubmed/11308263
http://dx.doi.org/10.1054/bjoc.2000.1707
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