| The role of B cell-mediated T cell costimulation in the efficacy of the T cell retargeting bispecific antibody BIS20x3. | |
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MedLine Citation:
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PMID: 15528335 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In this study, we investigated the role of the naturally occurring B cell-mediated T cell costimulation in the antitumor efficacy of the bispecific Ab BIS20x3. BIS20x3 has a dual specificity for both CD20 and CD3 and has previously been shown to effectively direct the lytic potential of cytolytic T cells toward malignant, CD20(+) B cells. BIS20x3 instigated T cell-B cell interaction caused a dose-dependent activation of T cells that was 30 times stronger when compared with T cell activation induced by monovalent anti-CD3 Abs. The activation of T cells by BIS20x3 and B cells appeared functional and resulted in the rapid induction of high lytic potential in freshly isolated peripheral T cells. BIS20x3-mediated T cell-B cell interaction resulted in a significant up-regulation of ICAM-1 on B cells and the activation of T cells was found to be dependent on the interaction of ICAM-1 with LFA-1 and trans-activation by the NF-kappaB pathway. Also, the lytic potential of freshly isolated T cells activated via BIS20x3 appeared to be dependent on NF-kappaB signaling in the target B cells. Interestingly, the costimulatory signaling effects described in this study appeared specifically related to the targeting against CD20 because targeting against CD19, by a CD3xCD19-directed bispecific Ab, was significantly less effective in inducing T cell activation and T cell-mediated B cell lysis. Together these results demonstrate that the malignant B cells actively contribute to their own demise upon CD20-directed bispecific Ab-mediated T cell targeting. |
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Authors:
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Alja J Stel; Bart-Jan Kroesen; Susan Jacobs; Herman Groen; Lou F M H de Leij; Hanneke C Kluin-Nelemans; Sebo Withoff |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 173 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2004 Nov |
Date Detail:
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Created Date: 2004-11-05 Completed Date: 2004-12-17 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 6009-16 Citation Subset: AIM; IM |
Affiliation:
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Department of Pathology and Laboratory Medicine, Section Medical Biology-Laboratory Tumor Immunology, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. A.J.Stel@med.rug.nl |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies, Bispecific
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metabolism,
therapeutic use* Antibodies, Monoclonal / metabolism, therapeutic use* Antigens, CD20 / immunology, physiology Antigens, CD3 / immunology, metabolism, physiology Antineoplastic Agents / metabolism, therapeutic use B-Lymphocytes / immunology*, metabolism, pathology* Cell Death / immunology Cell Line, Transformed Cell Line, Tumor Cross-Linking Reagents / metabolism, therapeutic use G0 Phase / immunology Humans Intercellular Adhesion Molecule-1 / metabolism, physiology Jurkat Cells Lymphocyte Activation / immunology* Lymphocyte Cooperation / immunology Lymphocyte Function-Associated Antigen-1 / metabolism, physiology NF-kappa B / genetics, metabolism Signal Transduction / immunology T-Lymphocytes / cytology, immunology*, metabolism Transcription, Genetic / immunology |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Bispecific; 0/Antibodies, Monoclonal; 0/Antigens, CD20; 0/Antigens, CD3; 0/Antineoplastic Agents; 0/Cross-Linking Reagents; 0/Lymphocyte Function-Associated Antigen-1; 0/NF-kappa B; 126547-89-5/Intercellular Adhesion Molecule-1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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